Gemzar (Gemcitabine) Uses, treatments, Indications, Side Effects and Warnings

Gemzar (Gemcitabine)
Potential health benefits on cancers and
research finds 2007

Gemcitabine, a pyrimidine nucleoside antimetabolite, is one of the
most promising new cytotoxic agents. The drug has shown activity
in a variety of solid tumors, and has been approved for the
treatment of non-small cell lung cancer, pancreatic, bladder,
ovarian, and breast cancer in Italy. [8]

Gemcitabine, a nucleoside analogue, an antimetabolite incorporated
as a triphosphate into DNA, has shown broad clinical benefits in
cancer conditions and it is currently used for the treatments of
non-small-cell lung cancer and pancreatic cancer in Japan. [3] In a
German study, a group receiving Gemzar, or gemcitabine, lived on
average of 13.4 months without their cancer reoccurance. While a
group that did not receive the drug lived without disease for 6.9
months. [1]

In the US, the drug uses are to fight breast, lung and ovarian cancer.
It is also used to treat inoperable pancreatic cancer. It costs about
$2,800 a month and has relatively mild side effects such as fatigue
and hair thinning. [1]

FDA has approved gemcitabine HCL for patients with advanced
pancreatic cancer who are not candidates for surgery in 1995. [2]
About 27,000 people in the United States were diagnosed with
pancreatic cancer in l994. Pancreatic cancer is generally
asymptomatic until late in the course of the disease. It is among the
most difficult cancers to treat and is rarely curable.

Before the FDA approval, Eli Lilly and Co. carried out two trials in
patients with
pancreatic cancer, one a comparison with 5 fluorouracil (5-FU) in
previously untreated patients; the other a study in 5-FU failures. The
studies measured tumor shrinkage, survival and an overall estimate
of clinical benefit (pain and ability to function).

Both studies showed a small rate of tumor shrinkage (about 7
percent); there was a small (about one and a half months)
improvement in median survival in the study comparing gemcitabine
with 5-FU. In both studies gemcitabine treated patients experienced
an approximately 25 percent rate of clinical response.

The 1 year survival rates in the comparative trial were 18 percent
and 2 percent for gemcitabine and 5-FU respectively. A second
phase II trial included patients who had not responded to 5-FU
treatment. Symptoms improved in 27 percent of patients, with a
median survival time of 3.85 months and a one year survival rate of
4 percent. A partial response rate (50 percent or greater decrease
in tumor size) was observed in 7.9 percent with disease stabilization
reported in 31.7 percent.

The major side effects of gemcitabine included neutropenia, a
decrease in white blood cells, which increases susceptibility to
infection; thrombocytopenia, a decrease in blood platelets, which can
cause excessive bleeding; and elevation of liver enzymes.

Nausea, vomiting, rash, flu-like symptoms, breathing difficulties and
traces of blood and protein in the urine have been reported. Rarely,
hemolytic-uremic syndrome (anemia associated with kidney failure)
was reported. Users should consult with their doctors on the possible
beneficial outcomes, risks, warning and side effects before using any
drug products.

How does gemcitabine benefit patients with breast cancer?
Gemcitabine is a single agent in first- and subsequent-line treatment
of breast cancer, with an overall objective response rate of 26%. It is
relatively well tolerated, and its dose-limiting toxicity has usually been
neutropenia. Gemcitabine has proven active in combination with
paclitaxel and, on this basis, a phase III trial showed a significantly
higher response rate than paclitaxel alone (39.3% v 25.6%). The
combination also showed a significantly longer median time to
progression (5.2 v 2.9 months) and significantly improved median
overall survival time (18.5 v 15.8 months). [4]

How may gemcitabine help patients with ovarian cancer?
The combination of paclitaxel and carboplatin is established as the
standard first-line chemotherapy regimen for advanced ovarian
cancer. Researchers consider to integrate gemcitabine into the
therapy for those with disease resistant to treatment with paclitaxel
plus carboplatin. [5] Researchers at University of Brescia, Italy say,
first-line combination chemotherapy including gemcitabine has
shown promising response rates in phase I and II studies. [6]

How may gemcitabine help patients with pancreatic cancer?
Pancreatic cancer (PCa) is one of the most lethal malignancies in
humans. Gemcitabine is the current standard chemotherapy of
advanced pancreatic cancer. Researchers found that several
tyrosine kinases --such as EGFR, VEGFR, PDGFR and Src--are
known to be overexpressed or constitutively activated in pancreatic
cancer. Hence, cetuximab and erlotinib, the monoclonal antibodies
against EGFR-1 (ErbB-1) showed promising activity in Phase II and
Phase III trials and their combination with gemcitabine resulted in
synergistic antitumor activity. [7]

How may gemcitabine help patients with non-small cell lung
cancer?
Approximately 30-40% of non-small cell lung cancer patients will
present with metastatic disease, and its associated poor prognosis.
Platinum-based chemotherapy has been shown to produce definite
improvements in efficacy and quality of life and is now the standard
of care.

Studies have shown that platinum combinations with third-generation
cytotoxics have shown additional gains in survival rates. Gemcitabine
and carboplatin is a well-tolerated regime. [9]

Gemcitabine is one of the most active agents for the treatment of
NSCLC. When combined with a platinum analog, gemcitabine
produces the best progression-free survival outcome of any
platinum-based regimen in first-line advanced NSCLC treatment
setting. [10]

How may gemcitabine help patients with cholangiocarcinoma
and gallbladder cancer?
In a phase II study, surgery offers the best chance for survival of
patients with gallbladder cancer or cholangiocarcinoma and should
remain the first treatment of choice. For patients not considered
candidates for surgery, but willing and able to tolerate chemotherapy
alone or in combination with a fluoropyrimidine (such as
5-fluorouracil or capecitabine), gemcitabine appears to be a
reasonable alternative to best supportive care. [11]

How may gemcitabine help patients with pancreatic
carcinoma?
Single-agent gemcitabine remains the standard treatment for
advanced pancreas cancer, based on results of four phase III trials
reported in 2004. [12]

Please, note that tons of research studies have done with
gemcitabine. The story above is incomplete. Disccuss with your
doctor for details. Consult with your doctor before taking a drug
product. This article is for information only.

[1] CARLA K. JOHNSON, Associated Press, Drug may delay pancreatic cancer return Jan 16, 2007 [2] Susan M. Cruzan FDA
AUTHORIZES TREATMENT IND FOR ADVANCED PANCREATIC CANCER FDA Feb. 17, l995 [3] Tsukagoshi S.
Gemcitabine is an effective single agent for the treatment of advanced biliary tract cancer Gan To Kagaku Ryoho. 2006
Sep;33(9):1365-9. [4] Smith IE. Overview of gemcitabine activity in advanced breast cancerSemin Oncol. 2006 Jun;33(3 Suppl
9):S19-23. [5] Thigpen T. The role of gemcitabine in first-line treatment of advanced ovarian carcinoma. Semin Oncol. 2006
Apr;33(2 Suppl 6):S26-32. [6] Pecorelli S, et al, Optimizing gemcitabine regimens in ovarian cancer. Semin Oncol. 2006 Apr;33(2
Suppl 6):S17-25. [7] Kleespies A, Jauch KW, Bruns CJ. Tyrosine kinase inhibitors and gemcitabine: new treatment options in
pancreatic cancer? Drug Resist Updat. 2006 Feb-Apr;9(1-2):1-18. Epub 2006 Apr 18. [8] Toschi L, et al, Role of gemcitabine in
cancer therapy. Future Oncol. 2005 Feb;1(1):7-17. [9] Saha A, Rudd R. Gemcitabine and carboplatin: is this the best combination
for non-small cell lung cancer? Expert Rev Anticancer Ther. 2006 Feb;6(2):165-73. [10] Natale R. A ten-year review of progress in
the treatment of non-small-cell lung cancer with gemcitabine. Lung Cancer. 2005 Oct;50 Suppl 1:S2-4. [11] Dingle BH, et al The
role of gemcitabine in the treatment of cholangiocarcinoma and gallbladder cancer: a systematic review. Can J Gastroenterol.
2005 Dec;19(12):711-6. [12] Richards DA. Chemotherapeutic gemcitabine doublets in pancreatic carcinoma. Semin Oncol. 2005
Aug;32(4 Suppl 6):S9-13.