Progress in Cancer Chemotherapy
This timeline of advances in cancer chemotherapy was developed by the American Society of Clinical Oncology
(ASCO), which represents nearly 30,000 physicians who treat people with cancer and research new cures. An
interactive version, which includes timelines of advances against a range of common cancers, is available online at
www.CancerProgress.Net.
Overview
Early chemotherapy regimens – beginning with nitrogen mustard for Hodgkin lymphoma in 1949 – improved
patient care but often came with side effects so severe that they required hospitalization. Today, dozens of
chemotherapy drugs, combined with more effective side-effects management, can cure an increasing number of
cancers, improve survival for many, and dramatically improve quality of life.
The earliest curative successes with chemotherapy occurred in patients with blood and lymphatic cancers. By the
late 1970s, combinations of drugs were used to help cure some patients with testicular and other “solid” tumors.
Since then, adjuvant chemotherapy – providing drugs after cancer surgery to help prevent cancer recurrence – has
radically improved the outlook for people with common early-stage cancers, including colon, breast and lung
cancer. Today, the use of neo-adjuvant chemotherapy – giving drugs before surgery to shrink tumors – is extending
the lives of patients whose cancer would once have been considered inoperable.
Timeline
1947 Leukemia
First-ever remission of pediatric leukemia
Sidney Farber, a physician at Children’s Hospital Boston, achieves the first partial remission of pediatric
leukemia in a 4-year-old girl using the drug aminopterin. He soon documents 10 cases of remission in a
landmark scientific paper. Until this time, children with acute leukemia usually died within weeks of
being diagnosed. While early remissions prove temporary, they pave the way for therapies that cure
thousands of patients in the decades to come, allowing most childhood cancer patients to live long,
healthy lives.
1949 First chemotherapy drug approved for cancer
Following results of clinical trials conducted in 1946 and 1947, nitrogen mustard is approved by the
Food and Drug Administration (FDA) for the treatment of Hodgkin lymphoma. Nitrogen mustard – also
known as mustard gas and stockpiled as a weapon in World War II – kills cancer cells by modifying
their DNA through a process called alkylation. Its discovery spurs rapid advancements in
chemotherapy, and the drug still receives some use today in combination chemotherapy for Hodgkin
lymphoma.
Progress in Cancer Chemotherapy
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1950s Colorectal Cancer
5-FU becomes mainstay of chemotherapy for colorectal cancer
Researchers begin using the chemotherapy drug 5-fluorouracil (5-FU) in patients with advanced
colorectal cancer, following promising data on the drug in other cancer types. Over the following
decades, researchers continue to refine 5-FU dosing and administration to maximize its effectiveness
and manage the often-intense side effects of the drug. 5-FU remains a mainstay of treatment for
colorectal cancer and has helped cure thousands of patients when used in combination with other
treatments, including radiation, surgery and other chemotherapy drugs.
1958 Leukemia
Pioneering “combination chemotherapy” cures leukemia
NCI scientists demonstrate that combination chemotherapy – in which multiple drugs are administered
together – can cause remissions in both children and adults with acute leukemia. Their findings set the
stage for nearly all modern chemotherapy, in which drug combinations, dosing and scheduling have
been carefully refined to maximize effectiveness while minimizing side effects.
1960 Testicular Cancer
First effective chemotherapy found for men with advanced testicular cancer
Doctors develop the first effective chemotherapy regimen for testicular cancer, using a combination of
the drugs actinomycin D, chlorambucil (Leukeran) and methotrexate. This combination causes tumors
to shrink in as many as half of patients whose disease has metastasized (spread to other parts of the
body).
1961 Leukemia
FDA approves new chemotherapy drugs vinblastine and vincristine
Vinblastine (Velban, Velsar) is approved after researchers demonstrate that the drug blocks a key
protein involved in cancer cell division and induces some leukemias and lymphomas into remission.
Vincristine (Oncovin), a sister drug to vinblastine, is approved in 1963. These drugs are in a family of
chemotherapies called “microtubule drugs,” and further investigation leads to the development of
similar, more effective and sometimes less toxic drugs for leukemia and other cancers, including
lymphoma, breast cancer, ovarian cancer and others.
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1961 Melanoma
Innovative technique enables intensive chemotherapy without increased systemic
side effects
A new approach known as isolated limb perfusion is introduced to help doctors deliver higher-thanusual
doses of chemotherapy to an arm or leg where melanoma tumors have spread, without
increasing the risk that the drugs will harm other parts of the body. During this procedure, the doctor
temporarily stops the flow of blood to and from the affected limb, essentially isolating it with a
tourniquet from the rest of the body, and then intravenously administers and circulates chemotherapy
through the affected limb with the help of a special machine. The approach is further refined in the
1990s with the introduction of isolated limb infusion, which cuts procedure time, requires fewer
specialized medical personnel and is less costly. Investigations continue to try to find better treatments
using this technique.
1960s Leukemia
Cytarabine provides major boost to combination chemotherapy for acute
myelocytic leukemia
Various studies show that the drug cytarabine (ara-C) has activity against leukemias and is highly
effective for treating a type of the disease known as acute myelocytic leukemia. Over time, the drug
becomes a critical component of chemotherapy for adults and children with this form of leukemia, and
researchers learn that precise timing and dosing of the drug is critical to successful treatment. The
drug is still widely used today, often in combination with other chemotherapy drugs.
1965 Lymphoma
Chemotherapy found to cure Hodgkin lymphoma
Researchers led by Vincent DeVita discover that a new chemotherapy regimen called MOPP
(mechlorethamine, vincristine, procarbazine and prednisone) cures up to 50 percent of patients with
advanced Hodgkin lymphoma. This regimen quickly becomes the standard treatment. In the 1970s, a
different chemotherapy combination (doxorubicin, bleomycin, vinblastine and dacarbazine – known as
ABVD) proves even more effective, curing about 70 percent of patients with advanced Hodgkin
lymphoma. The ABVD combination remains a mainstay of treatment today.
1967 Pediatric Cancer
Treating central nervous system helps achieve first cures for the common
childhood leukemia
Researchers at St. Jude Children’s Research Hospital first show that adding central nervous system
radiation and intrathecal therapy (chemotherapy that is injected into the fluid-filled space between the
layers of tissue that cover the brain and spinal cord) to standard chemotherapy, provides prolonged
remissions and the first long-term cures for acute lymphocytic leukemia (ALL). ALL is the most common
form of childhood leukemia.
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1970 Testicular Cancer
Two new drugs produce first complete remissions in advanced testicular cancer
Clinical trials show that the drugs vinblastine (Velban, Velsar) and mithramycin are effective in men
with advanced stages of testicular cancer. By combining the new drugs with existing treatments,
physicians find that they can achieve complete remissions in 10 to 20 percent of cases – an impressive
result for any cancer at an advanced stage.
1966-1977 Prostate Cancer
First standard chemotherapy regimens for prostate cancer
The National Prostate Cancer Project develops the first chemotherapy protocols to guide the use of
existing drugs for men with prostate cancer that has spread to other parts of the body (metastatic
disease).
1970s Brain Cancer
First promising chemotherapy for glioma
Researchers report the first data on efficacy of the chemotherapy drug carmustine (BCNU). Unlike other
chemotherapy drugs available at the time, carmustine is able to cross the blood-brain barrier and
directly attack gliomas. Although this drug can cause significant side effects, the first trials show that it
shrinks some tumors. Later trials show that carmustine and other similar drugs also provide a small but
significant increase in long-term survival when used with other treatments.
1974 Breast Cancer
Doxorubicin active against advanced breast cancer
The first studies of the chemotherapy drug doxorubicin (Adriamycin) in breast cancer demonstrate that
the drug can shrink breast tumors in women with advanced disease. Doxorubicin remains a mainstay
of treatment for breast cancer today, often in combination with other drugs (such as
cyclophosphamide, paclitaxel or docetaxel).
1974 FDA approves doxorubicin, a vital part of combination chemotherapy
Doxorubicin (Adriamycin), an anticancer antibiotic, is widely used to treat many cancers, including
Hodgkin lymphoma and some leukemias. It is also routinely used to treat cancers of the bladder,
breast, stomach, lung, ovaries, thyroid and other organs. Doxorubicin and similar drugs
(anthracyclines) are now considered the backbone of chemotherapy to cure diffuse large B-cell
lymphoma, the most common type of aggressive lymphoma.
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1974 Testicular Cancer
Antibiotic bleomycin helps reduce treatment-related side effects
Bleomycin (Blenoxane), an anticancer antibiotic, is approved by the FDA, and soon becomes part of
standard treatment for testicular cancer. The new drug is found to be an ideal component of
combination chemotherapy because, unlike other anticancer drugs, it does not suppress the bone
marrow’s ability to produce red and white blood cells. Patients who are able to maintain higher blood
cell counts are far less likely to experience treatment-related complications.
Mid-1970s Lung Cancer
Chemotherapy combinations prove effective in small cell lung cancer
Researchers show that a treatment regimen involving the drug doxorubicin (Adriamycin), together with
cyclophosphamide (Cytoxan), vincristine (Oncovin), and radiation therapy, causes significant tumor
shrinkage in some patients with early-stage small cell lung cancer. These findings lead to many
additional studies testing various chemotherapy combinations for this disease.
1975 Breast Cancer
Adjuvant chemotherapy increases cure rates for early-stage breast cancer
After overcoming concerns in the cancer community about whether the benefits outweigh the risks,
Drs. Bernard Fisher and Gianni Bonadonna demonstrate that chemotherapy after surgery – known as
adjuvant chemotherapy – prolongs the lives of women with early stage breast cancer. Their studies
explore use of the drugs 1-phenylalanine mustard or a combination of cyclophosphamide,
methotrexate and fluorouracil. Over time, adjuvant chemotherapy becomes a major component of
treatment for the disease, improving survival and cure rates in the years ahead. Today, about 9 in ten
women with early stage breast cancer are alive five years after their diagnosis.
This research also sets the stage for research on adjuvant therapy in other common cancers, including
colon and lung cancer, making it one of the most important advances in modern cancer care.
1975 Lymphoma
New chemotherapy regimen boosts Hodgkin lymphoma cure rates to 70 percent
Researchers led by Gianni Bonnadonna find that a new chemotherapy combination of doxorubicin
(Adriamycin), bleomycin (Blenoxane), vinblastine (Velban, Velsar) and dacarbazine (known as ABVD) is
more effective than the older MOPP combination regimen, and causes fewer side effects. Originally
developed for use as a treatment when MOPP no longer worked, ABVD quickly becomes the standard
of care when it’s found to cure approximately 70 percent of patients with advanced stage Hodgkin
lymphoma.
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1975 Pediatric Cancer
Successful use of adjuvant therapy in osteosarcoma
Researchers find that adjuvant chemotherapy – treating cancer with chemotherapy following surgery
for early-stage cancers – offers major benefits for children with osteosarcoma (cancer of the bone).
This approach prolonged the time that most patients in the study remained free of cancer recurrence
after their surgery. In 1986, results from a long-term randomized trial establish adjuvant chemotherapy
as the standard of care for all children with osteosarcoma.
1976 Lymphoma
CHOP regimen boosts cure rates for non-Hodgkin lymphoma
A combination of cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), vincristine (Oncovin) and
prednisone (CHOP) is shown to cure some patients with aggressive non-Hodgkin lymphoma. The
introduction of CHOP chemotherapy boosts cure rates to 40 to 50 percent for this otherwise very
aggressive and fatal form of lymphoma. In more recent years, cure rates have climbed to
approximately 90 percent for some types of lymphoma, with the addition of the targeted drug
rituximab (Rituxan) to the regimen – a combination called R-CHOP.
1977 Breast Cancer
Breakthrough drug, tamoxifen, receives initial FDA approval
The chemotherapy drug tamoxifen (Novaldex) is approved for the treatment of advanced breast
cancer, based on studies showing the drug caused significant tumor shrinkage. Tamoxifen blocks the
activity of estrogen, a hormone that fuels the growth and spread of many breast tumors. Over the next
two decades, the FDA approves additional uses of tamoxifen, including as a preventative for breast
cancer, based on clinical trials that provide a deeper understanding of which women are most likely to
benefit. Researchers also learn that the drug is only effective in women whose tumors contain
receptors for the hormones estrogen and/or progesterone – a finding that spares women without
these receptors from the unnecessary side effects of the drug.
1977 Leukemia
Chlorambucil induces remissions for chronic lymphocytic leukemia
Researchers demonstrate that the chlorambucil (Leukeran) can slow the progression of chronic
lymphocytic leukemia, the second most common type of leukemia in adults. In the late 1980s and early
1990s, a second drug called fludarabine (Fludara) is introduced, and proven effective for patients who
do not respond to chlorabucil.
1977 Testicular Cancer
New treatment regimen cures majority of advanced testicular cancers
A pivotal trial shows that combining the drugs cisplatin, vinblastine (Velban, Velsar) and bleomycin
(Blenoxane) (a regimen referred to as PVB) provides full remissions for 70 percent of patients with
advanced testicular cancer. Cisplatin is approved by the FDA the following year, and remains a
mainstay of testicular cancer treatment today.
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1978 Ovarian Cancer
First effective combination chemotherapy regimen for ovarian cancer
Researchers led by Robert Young develop a combination chemotherapy regimen for advanced ovarian
cancer, known as HEXACAF. This regimen combines the drugs hexamethylmelamine,
cyclophosphamide (Cytoxan), methotrexate and 5-fluorouracil, each of which was already known to
have an effect on ovarian cancer tumors. The combined regimen is found to benefit more patients,
cause greater tumor shrinkage and extend survival by more than 12 months over single-drug
chemotherapy with melphalan (Alkeran), an earlier drug commonly used to treat advanced ovarian
cancer. However, this new combination regimen causes significantly more side effects.
1978 Ovarian Cancer
Cisplatin approved for advanced ovarian cancer
The chemotherapy drug cisplatin becomes available as a treatment for newly-diagnosed ovarian
cancer, as well as ovarian cancer that persists after initial therapy, after trials show the drug decreases
the size of patients’ tumors. Later research leads to the development of new and more effective
combination chemotherapy regimens that utilize cisplatin, such as cyclophosphamide (Cytoxan) plus
cisplatin and a regimen called CHAP, which combines the drugs doxorubicin (Adriamycin),
hexamethylmelamine, cyclophosphamide and cisplatin.
1981 Pancreatic Cancer
Chemotherapy plus radiation effective for patients who cannot be treated
surgically
Adding the chemotherapy drug 5-fluorouracil to standard radiation is shown to boost one-year survival
from 10 percent to 40 percent for patients with locally advanced inoperable pancreatic cancer (disease
that has spread to nearby tissues but cannot be surgically removed). The findings show the benefits of
combining different treatment approaches for this stage of disease.
1982 Leukemia
Daunorubicin proven superior to doxorubicin for AML
Large trial shows that using the anthracycline drug daunorubicin (Cerubidine, Rubidomycin), in
combination with cytarabine (ara-C), is more effective at causing complete remissions of acute
myelocytic leukemia – one of the most common leukemias in adults – than the previous standard drug,
doxorubicin (Adriamycin). Over the following decade, researchers evaluate similar drugs, such as
idarubicin (Idamycin), that provide similar, and possibly better, remission rates.
1982 Prostate Cancer
Early hormone therapy drugs introduced
Studies demonstrate the effectiveness of treatments known as luteinizing hormone receptor hormone
antagonists (LHRHa therapy). These drugs – the first of which is approved by the FDA three years later –
chemically reduce the production of testosterone and are used to slow the growth of prostate cancer,
which is fueled by male sex hormones. The new approach is reversible, and thus preferable to the
other options available at the time, including surgical removal of the testicles. Hormone therapy is now
a standard approach for treating the disease.
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1985 Pancreatic Cancer
Chemotherapy plus radiation effective as adjuvant therapy
For patients with earlier stage disease, giving a combination of the chemotherapy drug 5-fluorouracil
and radiation following surgery (referred to as adjuvant therapy) is shown to improve median survival
by nearly a year compared to surgery alone.
1986 Breast Cancer
Tamoxifen reduces breast cancer recurrence
Tamoxifen is approved as adjuvant therapy for post-menopausal women following breast cancer
surgery, based on studies showing that use of the drug for five years after surgery reduces the risk of
cancer recurrence and dramatically increases survival.
1987 Pediatric Cancer
Chemotherapy before surgery helps children with bone cancer avoid amputation
A clinical trial shows that giving chemotherapy before surgery to remove tumors, an approach called
neo-adjuvant chemotherapy, is effective for children with osteosarcoma (cancer of the bone). In many
cases, this approach enables surgeons to remove tumors without fully amputating a limb, and without
compromising the overall effectiveness of treatment.
1987 Testicular Cancer
Researchers hone standard chemotherapy to increase effectiveness, minimize side
effects
A new standard of care is established when a trial shows that using the drug etoposide (Toposar,
VePesid), instead of vinblastine (Velban, Velsar), together with cisplatin and bleomycin (Blenoxane)
leaves more patients cancer-free and causes far fewer nerve and muscular side effects. Over time,
researchers also learn that many men respond well to three cycles of chemotherapy, rather than four,
and that patients who do relapse can generally be cured with one additional round of chemotherapy.
1987 Testicular Cancer
Some testicular cancer patients can forego chemotherapy
Studies show that many men with early-stage testicular cancer can forego chemotherapy after surgery,
and instead receive “active surveillance” (regular check-ups to monitor for cancer recurrence). When
cancer does recur, available drugs are generally able to cure the disease. This approach spares many
men from the side effects of possibly unnecessary chemotherapy, and is now the standard approach
for about 75 to 80 percent of patients.
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Late 1980s Pediatric Cancer
Improved combination chemotherapy regimens boost pediatric leukemia cure
rates
Cure rates for pediatric acute lymphoblastic leukemia (ALL) climb above 80 percent with the
introduction of combination chemotherapy regimens.
In the same time period, cancer remissions (which may or may not be permanent) also climb as high as
99 percent, with the help of ongoing advances in supportive care. Supportive care dramatically eases
the side effects of treatment and enables greater numbers of patients to complete their full
chemotherapy regimen on schedule.
1989 Ovarian Cancer
FDA approves carboplatin for ovarian cancer
The chemotherapy drug carboplatin (Paraplatin, Paraplat) becomes available as a second line of
therapy for ovarian cancer, after research shows that it promotes tumor shrinkage. It becomes
available as an initial therapy two years later, after being shown to increase survival. This approval
offers an effective treatment alternative for patients who cannot tolerate the standard chemotherapy
drug, cisplatin, which carries significant side effects. It later becomes the preferred initial
chemotherapy, after studies show it is as effective as cisplatin but causes fewer side effects.
1985-1991 Colorectal Cancer
Treatment after surgery increases colorectal cancer survival
Doctors begin administering chemotherapy following surgery (adjuvant treatment) to patients with
colon and rectal cancer whose disease has spread within the wall of the colon and to nearby lymph
nodes (stage III), after clinical trials show that the approach improves survival and significantly reduces
the risk of cancer recurrence. Adjuvant therapy becomes a mainstay of colon cancer treatment after a
U.S. National Institutes of Health expert panel recommends the approach in 1990. Previously, about
half of patients experienced a recurrence of their cancer after surgery, which often led to death.
Adjuvant therapy was found to reduce the risk of recurrence and improve survival by about 40 percent.
1990-1992 Lung Cancer
Combining chemotherapy and radiation prolongs survival for non-small cell lung
cancer
Two studies show that treatment programs involving both radiation and chemotherapy are more
effective than either approach alone for patients with “stage III” non-small cell lung cancer (including
patients with larger tumors that may or may not have limited spread within the lungs and in nearby
lymph nodes). This two-pronged treatment approach soon becomes the standard of care for this
disease.
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1992-1994 Breast and Ovarian Cancer
Taxanes emerge as a vital chemotherapy option for ovarian, breast cancer
A new family of treatments debuts with the FDA approval of paclitaxel (Taxol) for advanced ovarian
cancer. The drug receives one of the fastest-ever approvals, on the heels of data showing it shrinks
ovarian tumors by more than half in many women who had stopped responding to all other therapies.
Later studies show it extends survival by over a year when used as an initial therapy for advanced
ovarian cancer, along with the chemotherapy drug cisplatin.
Over the next decade, paclitaxel also proves effective for all stages of breast cancer – extending lives
and delaying disease progression compared to existing therapies, and delaying recurrence when used
as adjuvant therapy (after surgery). The drug is derived from the bark of a yew tree, and is the product
of a field of research exploring ‘natural’ cures for a range of diseases. Until drugmakers discovered a
synthetic method for producing the drug, there was widespread concern that the natural resources
needed to produce the drug would not meet demand.
1993 Brain Cancer
Adding chemotherapy to radiation after surgery increases survival for malignant
gliomas
A large analysis of the results of several studies shows that adding chemotherapy to radiation therapy
helps patients with surgically treated malignant gliomas live longer compared to radiation therapy
alone. Randomized trials had previously found that this approach yielded only marginal benefits, yet
when the data from these individual studies were assessed in combination, the survival advantage
became more pronounced. Despite this result, the still-modest benefits of the combination approach,
and the potential for serious side effects, have led to continued debate about its use.
1993 Lung Cancer
Simultaneous radiation and chemotherapy boosts survival for small cell lung
cancer
Researchers demonstrate that starting radiation therapy together with chemotherapy dramatically
improves the effectiveness of treatment for patients with early-stage small cell lung cancer, compared
to starting radiation later in the course of treatment. This new approach is found to significantly delay
cancer progression and improve survival.
Mid-1990s Lung Cancer
New generation of chemotherapy drugs for non-small cell lung cancer
Within just a few years, several new chemotherapy drugs for non-small cell lung cancer are shown to
be effective, particularly when combined with cisplatin. These new drugs include paclitaxel (Taxol),
docetaxel (Taxotere), vinorelbine (Navelbine) and gemcitabine (Gemzar). Randomized studies show
that regimens containing these drugs provide comparable levels of efficacy for patients with advanced
disease.
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1995 Leukemia
Approval of tretinoin leads to 95 percent cure rate for rare leukemia
Tretinoin (Vesanoid), a drug related to vitamin A, is found to cause remission in patients with acute
promyelocytic leukemia (APL), a rare form of leukemia. It may be given alone or in combination with
other drugs in patients whose disease has recurred after previous therapy. The discovery of the drug is
fueled by the realization that this form of leukemia develops when cells do not mature properly;
tretinoin is the first drug to correct this abnormal process. Prior to the availability of this drug, APL was
a rapidly progressing and often fatal illness. Today, patients are treated with a newer drug, called
arsenic trioxide, as well as tretinoin, and APL is considered one of the most curable forms of leukemia.
1995 Lung Cancer
Analysis affirms benefits of chemotherapy for advanced non-small cell lung
cancer
An analysis of data from more than 50 clinical trials sheds important new light on the benefits of
chemotherapy for advanced non-small cell lung cancer, concluding that cisplatin chemotherapy, in
addition to surgery, radiation therapy or supportive care, substantially extends survival. Prior to this
analysis, there was significant concern that the risks and side effects of chemotherapy outweighed the
limited benefits for patients with advanced disease. The authors of the analysis also suggest that giving
chemotherapy following the surgical removal of lung tumors – adjuvant chemotherapy, considered a
novel approach for lung cancer at the time – extends survival by as much as 5 percent. This finding
prompts the launch of several large clinical trials to test this ultimately successful new treatment
strategy.
1996 Colorectal Cancer
Irinotecan is approved for advanced colon cancer
The FDA approves irinotecan (Camptosar), given with the drugs 5-fluorouracil and leucovorin, for
patients with advanced colon cancer that has returned despite prior treatment. Irinotecan is the first
new chemotherapy drug approved for advanced colon cancer in roughly 40 years. Although prognosis
generally remains poor for patients with this stage of cancer (also called metastatic disease), the new
drug is shown to improve survival and help preserve quality of life.
1996 Lung Cancer
Topotecan approved as second round of treatment for small cell lung cancer
A study reports that topotecan (Hycamtin) is as effective as combination treatment with
cyclophosphamide (Cytoxan), doxorubicin (Adriamycin) and vincristine (Oncovin) for small cell lung
cancer that returns after initial therapy. It soon becomes a new standard of care. An oral formulation
of this drug is approved in 2007.
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1996 Ovarian Cancer
New chemotherapy drug for advanced ovarian cancer
Topotecan (Hycamptin) is approved to treat advanced ovarian cancer after other treatments have
failed, based on studies showing the drug increases survival. Topotecan is the first in a new class of
chemotherapy drugs called topoisomerase I inhibitors, which interfere with DNA replication to prompt
cancer cell death.
1996 Pancreatic Cancer
Gemcitabine modestly extends survival, relieves symptoms with advanced
pancreatic cancer
Gemcitabine (Gemzar) is approved for pancreatic cancer that has spread to nearby organs or to distant
parts of the body, based on a clinical trial demonstrating that it modestly extends survival compared to
5-fluorouracil, the previous standard of care. Gemcitabine is also shown to provide greater relief from
disease-related symptoms, including pain. Gemcitabine is widely used today to treat the disease, either
alone or in combination with other drugs.
1996 Prostate Cancer
New treatment for prostate cancer that resists hormone therapy
FDA approves the drug mitoxantrone (Novantrone) for men with advanced prostate cancer that does
not respond to hormone therapy. Approval is based on a randomized trial showing that adding the
drug to standard prednisone therapy improved quality of life, reduced pain, and caused greater
declines in PSA levels than prednisone therapy alone.
1997 Colorectal Cancer
Surgery found to cure some patients with advanced colorectal cancer
In general, metastatic cancer is difficult or impossible to treat with surgery because tumor cells have
spread throughout the body. But in a 1997 study, researchers find that some colon cancer patients
with tumors that have spread to the liver alone can be cured with surgery. In a study of nearly 300
such patients who underwent surgery between 1960 and 1987, about one in four were still alive five
years later, and nearly of all of these patients were found to have been essentially cured. A later study
finds that use of positron emission tomography, or PET scanning, can identify some liver metastases
that would have gone unnoticed before, helping surgeons in the study to achieve a cure rate above 50
percent for patients with metastatic disease.
1997 Prostate Cancer
Adding hormone therapy to radiation improves prostate cancer survival
Two pivotal studies show that adding hormone therapy before and after radiation therapy reduces the
risk that the cancer will spread and increases survival, when compared to radiation treatment alone.
This combination quickly becomes the standard approach.
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1998 Breast Cancer
Oral chemotherapy drug, capecitabine, approved for advanced breast cancer
Capecitabine (Xeloda) becomes an important treatment option for women whose breast cancer has
progressed despite other commonly used forms of chemotherapy. The drug is approved by the FDA
based on studies demonstrating the drug slows cancer progression. Unlike other traditional
chemotherapies that are administered intravenously, capecitabine is administered orally – a convenient
alternative that requires fewer doctor’s visits for patients with advanced cancer.
1998 Breast Cancer
Chemotherapy before surgery helps more women benefit from breast-conserving
treatment
A major trial reports that an approach called neoadjuvant chemotherapy – providing chemotherapy
before breast cancer surgery – allows more than two-thirds of women with large breast tumors to
undergo breast-conserving surgery, called lumpectomy, instead of full mastectomy. The goal of
neoadjuvant therapy is to shrink tumors so that less tissue needs to be removed surgically. Breastconserving
surgery, also called lumpectomy, is easier to recover from and results in far better cosmetic
outcomes – without compromising survival – compared with mastectomy. Neoadjuvant therapy is later
shown to benefit patients with rectal and other common cancers.
1998 Pediatric Cancer
New chemotherapy regimen reduces side effects for children with Hodgkin
lymphoma
A National Cancer Institute-funded study shows that a chemotherapy combination regimen known as
ABVD (with the drugs doxorubicin, bleomycin, vinblastine and dacarbazine) can safely replace the
previous standard treatment for patients with advanced Hodgkin lymphoma. This new combination
dramatically lessens the side effects of cancer therapy for children with the disease, without affecting
overall treatment outcomes.
1999 Brain Cancer
New oral chemotherapy drug, temozolomide, increases glioma survival
The FDA grants accelerated approval to the oral chemotherapy drug temozolomide (Temodar) to treat
anaplastic astrocytoma (a form of high-grade glioma) that recurs following other therapy. The
approval is based on early-stage data suggesting that the drug shrinks tumors and is generally well
tolerated. In 2005, temozolomide receives full approval for this and other high-grade gliomas, based
on data showing that adding the drug to initial radiation therapy increases two-year survival by as
much as 50 percent.
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1999 Cervical Cancer
NCI recommends chemotherapy-radiation combination for invasive cervical cancer
The National Cancer Institute issues an alert recommending that physicians consider adding
chemotherapy to radiation therapy for women being treated for invasive cervical cancer (cancer that
has spread within the cervix or pelvis). This updated approach is based on several randomized trials
showing that women lived longer when treated with both radiation and chemotherapy, compared to
those treated with the prior standard of radiation or surgery alone.
1999 Lung Cancer
Simultaneous chemotherapy and radiation proven most effective for stage III nonsmall
cell lung cancer
Researchers find that giving chemotherapy and radiation during the same treatment period, an
approach known as concurrent chemoradiation, results in better survival for patients with stage III
non-small cell lung cancer (disease with limited spread in the lungs and surrounding tissue) than the
standard practice of waiting to give radiation therapy until after chemotherapy was completed. This
finding echoes similar findings reported for small cell lung cancer in earlier years.
1999 Ovarian Cancer
FDA approves liposomal doxorubicin for advanced ovarian cancer
Liposomal doxorubicin (Doxil) receives accelerated FDA approval to treat advanced ovarian cancer that
has progressed after prior treatment. The drug is unique because the active chemotherapy agent is
encased in a microscopic fat bubble that releases the drug at the tumor site, delivering more of the
chemotherapy directly to the tumor and less to other parts of the body, thereby limiting side effects.
Full approval is granted in 2005 based on follow-up studies showing that the drug shrinks ovarian
tumors and extends survival compared to standard topotecan (Hycamptin) chemotherapy. By the end
of the 1990s, patients with advanced ovarian cancer have a growing number of chemotherapy options
to select from.
1999 Pediatric Cancer
Intensive chemotherapy, with radiation and stem cell transplantation, improves
neuroblastoma survival
An NCI study shows that treatment with intensive chemotherapy, together with radiation therapy and
autologous stem cell transplantation, lowers the risk of recurrence and improves survival in children
with high-risk neuroblastoma (a cancer of the nerve tissue). Adding stem cell transplantation to
neuroblastoma therapy makes it possible for patients to recover from the intense chemotherapy
needed to effectively fight the disease. In this approach, doctors harvest healthy stem cells from the
patient’s own bone marrow before chemotherapy and then re-implant them intravenously after
treatment. The infusion of stem cells helps rebuild the patient’s blood-production and immune system,
which are both impaired by chemotherapy.
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2000 Breast Cancer
High-dose chemotherapy plus stem cell transplant does not improve breast cancer
survival
In several large, randomized studies, researchers demonstrate conclusively that high-dose
chemotherapy with supportive stem-cell or bone marrow transplantation does not improve survival
among women with advanced breast cancer or earlier-stage cancer. These results immediately change
practice. (Based on the results of earlier small-scale studies, the approach came into widespread use for
both advanced and early-stage breast cancer patients – well before large, randomized clinical trials
were conducted.) The approach involves administering extremely high doses of chemotherapy to fight
the cancer, which had been used successfully in other cancers such as lymphoma and leukemia.
However, because such high doses destroy bone marrow, they are fatal if not supported by bone
marrow transplantation or stem cell support, which repopulate these vital cells. The negative trial
results underscore the importance of confirming preliminary data from uncontrolled pilot trials in more
definitive phase III studies.
2000 Leukemia
Fludarabine works faster, better for patients with CLL
A large, long-term clinical trial demonstrates that the drug fludarabine (Fludara) – originally developed
as a back-up therapy for patients with chronic lymphocytic leukemia – works in more patients and
produces longer-lasting remissions than the previous standard drug, chlorumbucil (Leukeran).
However, the drug only works reliably in patients younger than age 65, and stem cell transplantation
from a healthy, matched donor remains the only curative therapy for this disease.
2000 Lung Cancer
Second round of chemotherapy boosts survival in advanced non-small cell lung
cancer
Studies report that patients with advanced non-small cell lung cancer that worsens after prior
treatment with platinum-based chemotherapy (such as cisplatin or carboplatin) live significantly longer
when they receive additional docetaxel (Taxotere) chemotherapy than when they receive only
supportive care (treatment to ease their cancer-related symptoms, but not to fight their disease). These
are the first data to show a survival benefit from administering a second round of chemotherapy to
patients with advanced non-small cell lung cancer.
2001-2004 Colorectal Cancer
First oral chemotherapy drug helps simplify colon cancer treatment
The FDA approves capecitabine (Xeloda) for patients with advanced (metastatic) colon cancer, and
later for patients with stage III colon cancer (cancer with limited spread in the surrounding tissue) who
have had surgery to remove the tumor. Capecitabine is a pill version of the widely used intravenous
chemotherapy drug 5-fluorouracil that offers comparable effectiveness with a more convenient way for
patients to receive their treatment. Recently, capecitabine has been combined with the drug oxaliplatin
(Eloxatin) as an initial therapy for metastatic colon cancer and for early-stage colon cancer.
Progress in Cancer Chemotherapy
16
2002-2004 Colorectal Cancer
New “FOLFOX” chemotherapy effective for colon cancer
Oxaliplatin (Eloxatin) combined with 5-fluorouracil and leucovorin (a regimen called FOLFOX) is
approved to treat advanced colon cancer that has spread despite other treatments. FOLFOX is later
approved for stage III colon cancer (cancer involving the nearby lymph nodes) following surgery, after
a pivotal trial finds that it increased the time that patients live without their cancer returning (diseasefree
survival). Longer-term data from the same study found that the combination also extends
patients’ lives.
2003 Breast Cancer
Higher density, shorter term chemotherapy improves breast cancer survival
Studies show that dose-dense chemotherapy – giving a combination of chemotherapy drugs
(doxorubicin, cyclophosphamide and paclitaxel) for early-stage breast cancer every two weeks instead
of every three weeks – slowed cancer growth by 26 percent and extended survival by 31 percent
without increasing treatment-related side effects.
2003 Ovarian Cancer
New chemotherapy regimen – docetaxel and paclitaxel – provides important
treatment option
A large study finds that combination chemotherapy with docetaxel (Taxotere) and carboplatin
(Paraplatin, Paraplat) is as effective as the standard paclitaxel (Taxol) and carboplatin regimen for
newly diagnosed, advanced ovarian cancer. The docetaxel combination has different side effects than
the paclitaxel combination, offering patients a potential treatment alternative. However, docetaxel is
not FDA approved for ovarian cancer and has not been widely used for this purpose in the United
States.
2003 Pediatric Cancer
Adding two drugs to standard chemotherapy improves survival for children with
early-stage Ewing sarcoma
Scientists show that adding two additional drugs (ifosfamide and etoposide) to the standard four-drug
combination chemotherapy regimen (doxorubicin, vincristine, cyclophosphamide and dactinomycin)
significantly increases five-year survival rates in patients with early-stage Ewing sarcoma (a form of
bone cancer, that most often occurs in the legs, spine, ribs, or pelvis). This new combination soon
becomes the standard treatment.
Progress in Cancer Chemotherapy
17
2004 Breast Cancer
New class of drugs, aromatase inhibitors, introduced
The FDA approves the drug letrozole (Femara), the first in a new class of drugs called aromatase
inhibitors that block an enzyme the body needs to make estrogen (estrogen fuels the growth of some
breast cancers). The drug is first approved for long-term use in post-menopausal women who have
completed five years of tamoxifen (Novaldex) treatment, based on studies showing letrozole reduces
the risk of breast cancer recurrence and spread even more than tamoxifen alone. In 2005, letrozole is
also approved as an initial therapy following surgery for post-menopausal women.
In the same time period, additional trials show that aromatase inhibitors, including letrozole and
similar drugs like anastrazole (Arimidex), also improve survival and alleviate the symptoms of cancer for
post-menopausal women with advanced breast cancer.
2004 Breast Cancer
Adding new drug, gemcitabine, extends survival for some women with advanced
breast cancer
Researchers show that adding a new chemotherapy drug called gemcitabine (Gemzar) to standard
paclitaxel (Taxol) chemotherapy improves survival by several months for women with advanced breast
cancer. This treatment regimen is approved in the same year, for women whose cancer persists despite
other forms of chemotherapy.
2004 Breast Cancer
Docetaxel helps reduce breast cancer recurrence
Docetaxel (Taxotere), a chemical cousin of paclitaxel (Taxol) that blocks cell division, is shown to
decrease the risk of cancer recurrence by more than 25 percent and increase survival among women
with operable breast cancer that has spread to the lymph nodes, compared to the previous standard
therapy, fluorouracil. The FDA approval of docetaxel later the same year expands the arsenal of
chemotherapy drugs for women with breast cancer.
2004 Colorectal Cancer
Chemotherapy and radiation before surgery reduce side effects for rectal cancer
patients
Results from a large clinical study show that giving chemotherapy and radiation therapy before, rather
than after, rectal cancer surgery reduces the risk of local recurrence (cancer recurrence in the pelvis,
near the original tumor). Survival was similar in both approaches, but because the pre-surgery
treatment regimen was more tolerable, it is now the standard approach for treatment of rectal cancer.
2004 Adjuvant chemotherapy shown to benefit patients with early pancreatic cancer
The European Study Group for Pancreatic Cancer (ESPAC) finds that adjuvant use (after surgery) of the
chemotherapy drug 5-fluorouracil more than doubles 5-year survival for patients with early-stage
disease, compared to surgery alone. The findings resolve a long-running debate about the value of
adjuvant chemotherapy. The study also calls into question the need for adjuvant radiation following
surgery, since chemotherapy alone was effective. Researchers continue to address this question.
Progress in Cancer Chemotherapy
18
2004 New chemotherapy for hard-to-treat prostate cancers
The FDA approves the drug docetaxel (Taxotere) after two clinical trials show that it increases survival
in men who have prostate cancer that continues to grow despite standard hormone therapy. The new
drug offers hope for men with this hard-to-treat form of the disease.
2004 Single dose of chemotherapy reduces risk of cancer recurrence in men with earlystage
disease
A large European study shows that a single dose of the chemotherapy drug carboplatin (Paraplatin,
Paraplat), following surgical removal of the cancerous testicle, lowers the risk of cancer recurrence and
may reduce the risk of cancer developing in the opposite testicle. This finding results in a new
treatment option for men with early-stage testicular cancer, potentially sparing them from standard
radiation therapy, which is highly effective but is associated with an increased risk of developing a
second cancer in another organ later in life.
2004-2005 Adjuvant therapy proven effective in lung cancer
In findings that quickly change the standard of care, clinical trials show that giving chemotherapy after
surgery dramatically improves survival for patients with early-stage non-small cell lung cancer.
2005 Pediatric Cancer
New treatment option for children with rare forms of leukemia and lymphoma
The FDA approves the drug nelarabine (Arranon) for children with T-cell acute lymphoblastic leukemia
(T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) whose cancer has progressed or returned following
two prior chemotherapy regimens. Nelarabine is the first drug approved to exclusively treat this limited
group of patients.
2006 Brain Cancer
Genetic mutations affect survival for oligodendroglioma
Two studies find that patients with oligodendroglioma tumors (a form of glioma) that lack certain
parts of chromosomes 1 and 19 are more sensitive to treatment and have better survival than patients
whose tumors are not missing this genetic material. Both studies also evaluated the benefit of adding
chemotherapy to standard radiation, finding that this approach caused significant side effects and did
not improve survival in the overall population.
Progress in Cancer Chemotherapy
19
2006 Ovarian Cancer
Direct chemotherapy approach increases survival
Researchers report that adding intraperitoneal chemotherapy – delivering chemotherapy directly into
the abdomen through a catheter – to intravenous chemotherapy following surgery extends survival by
over a year for women with advanced ovarian cancer, compared to surgery and intravenous
chemotherapy alone. This report confirms two earlier studies and based on the combined findings, the
National Cancer Institute encourages physicians to discuss the newer approach with certain patients
with advanced disease. This combination regimen causes more side effects than intravenous
chemotherapy alone, including some that are life-threatening, so researchers continue to study lowerdose
and alternative drug approaches that provide may provide similar benefits with fewer side effects.
2007 Breast Cancer
First in new class of drugs approved for advanced breast cancer that resists other
treatments
The FDA approval of ixabepilone (Ixempra) offers a new treatment option to stop or slow the growth
of tumors in women whose advanced breast cancer no longer responds to any other chemotherapy.
The drug is used as a single therapy or in combination with the chemotherapy drug capecitabine.
Ixabepilone is part of a new class of chemotherapy drugs called epothilones, which fight the disease by
preventing cancer cells from dividing.
2007 Leukemia
Addition of an arsenic compound found to improve survival for rare form of
leukemia
A large clinical trial finds that adding arsenic trioxide (Trisenox) to the standard treatment for acute
promyelocytic leukemia (APL) improves survival for adults newly diagnosed with the disease. Arsenic
has historically been known as a potent poison, but its use in traditional Chinese medicine led to the
development of this drug. The drug is approved by the FDA later the same year.
2007 Leukemia
Bendamustine is effective against chronic lymphocytic leukemia (CLL)
Bendamustine (Treanda), a nitrogen mustard-based drug which has been used in Europe for decades,
is found to triple the time it takes for cancer to progress and produce more complete remissions than
the standard chemotherapy for chronic lymphocytic leukemia. Bendamustine is approved by the FDA
as an initial treatment for the disease in early 2008.
Progress in Cancer Chemotherapy
20
2007 Pediatric Cancer
Children with neuroblastoma benefit from less aggressive treatment
A large, international trial finds that some children with neuroblastoma (a cancer of the nerve tissue)
can receive a much less aggressive chemotherapy regimen than the previous standard treatment,
without reducing their survival. Reducing chemotherapy, surgery and radiation helps children avoid
serious, long-term side effects such as hearing loss. Today, certain key factors, such as age, stage of
the tumor and specific tumor characteristics help determine which children with neuroblastoma can
have reductions in therapy.
2007-2008 Pancreatic Cancer
Adjuvant gemcitabine further extends survival for patients with early pancreatic
cancer
Two important studies demonstrate that adjuvant (post-surgery) treatment with gemcitabine (Gemzar)
is beneficial. In one study, 6 months of gemcitabine doubled the average time it took for the disease to
come back and extended patients’ lives by nearly 3 months. In the other study, the addition of
gemcitabine to adjuvant 5-fluorouracil-based chemotherapy and radiation was also associated with a
survival benefit.
2009 Breast Cancer
Standard chemotherapy is an option for older women
Researchers find that chemotherapy with capecitabine (Xeloda) alone is less effective and is associated
with more serious side effects among older women with early-stage breast cancer than the three-drug
chemotherapy regimen that younger women typically receive. The finding resolves a long-running
debate about whether a single oral drug would be more tolerable or more effective than a
combination of drugs for older patients, showing that otherwise healthy elderly patients can tolerate
and benefit from the standard treatment regimen.
2009 Lung Cancer
Maintenance therapy improves survival for advanced non-small cell lung cancer
Large clinical trials show that patients with advanced non-small cell lung cancer who continued to
receive drug therapy after completing their initial chemotherapy regimen lived longer than patients
who did not receive such therapy. In separate studies, this finding is shown with the chemotherapy
drug, pemetrexed (Alimta) and with the targeted therapy erlotinib (Tarceva). Based on this research,
the FDA ultimately approves these agents for this use.
Progress in Cancer Chemotherapy
21
2010 Breast Cancer
Targeted drug denosumumab helps prevent common bone-related complications
in advanced breast cancer
About 80 percent of women with metastatic breast cancer experience cancer spread to the bone, a
complication that causes pain, bone weakening and other side effects that affect quality of life. In
2010, a large study shows that the targeted drug called denosumumab (Xgeva) can prevent or
significantly delay bone metastases. Other drugs, such as zoledronic acid (Zometa), have previously
been used to prevent and treat these bone-related complications, but this study suggests
denosumumab may be more effective.
2010 Breast Cancer
New chemotherapy drug improves survival for advanced breast cancer
A clinical trial finds that a new drug derived from a marine sponge, eribulin mesylate (Halaven),
prolongs survival by several months among women with breast cancer that has spread or returned
after previous treatment with conventional therapies. The FDA approves eribulin in November 2010 for
advanced breast cancer that persists despite prior treatment.
2010 Lung Cancer
Older patients should be considered for the same aggressive chemotherapy as
younger patients
Older patients have traditionally received less aggressive therapy than younger patients, out of concern
that they would not be able to handle the side effects. But a large study shows that a combination of
two commonly used chemotherapy drugs, paclitaxel (Taxol) and carboplatin (Paraplatin, Paraplat),
significantly increased survival in patients age 70 or older with advanced non-small cell lung cancer,
compared to the standard single-drug therapy used among older patients. The findings suggest that
older patients should be considered for the same aggressive combination therapy as younger patients.
2010 Ovarian Cancer
Pre-surgery chemotherapy proven an effective option for women with advanced
ovarian cancer
Major European trial reports that giving chemotherapy prior to surgery (called neo-adjuvant
chemotherapy) or after surgery (called adjuvant chemotherapy) is equally effective in women with
advanced ovarian cancer. These results resolve long-standing debate and provide an important
treatment alternative, particularly for women with larger tumors. In this group, giving chemotherapy
first can shrink the tumors so that less extensive surgery is needed later on in the course of therapy.
2010 New combination chemotherapy regimen extends advanced pancreatic cancer
survival
Major trial shows that initial treatment with FOLFIRINOX chemotherapy extends survival by nearly five
months in patients with advanced pancreatic cancer, compared with standard gemcitabine (Gemzar)
treatment. FOLFIRINOX combines the drugs 5-fluorouracil, leucovorin, irinotecan (Camptosar) and
oxaliplatin (Eloxatin). This is the largest observed survival advantage in a major clinical trial among
patients with advanced pancreatic cancer.
Progress in Cancer Chemotherapy
22
2010 New drug for patients whose disease progresses despite other treatments
The FDA approves cabazitaxel (Jevtana), given together with the drug prednisone, for men with
advanced stages of prostate cancer that has progressed despite prior hormone therapy and
chemotherapy with a drug called docetaxel (Taxotere). The approval, the first for this group of patients
who have few other options, was based on data showing cabazitaxel increases survival compared with
standard mitoxantrone (Novantrone) chemotherapy in patients who have already received docetaxel
treatment.
http://www.cancerprogress.net/downloads/timelines/progress_in_cancer_chemotherapy_timeline.pdf