Gemcitabine (Gemzar), recently approved by the FDA as a treatment
IND for patients with advanced or metastatic pancreatic cancer,
has shown promise in the treatment of non-small-cell lung cancer
(NSCLC), both as a single agent and in combination with other
chemotherapy drugs, Alan Sandler, md, reported at a symposium
held at the Chemotherapy Foundation meeting last year.
Structurally related to cytarabine (ara-C), gemcitabine accumulates
to a greater degree and is less readily eliminated from tumor
cells than ara-C. Incorporated into DNA, gemcitabine results in
chain termination and inhibits enzymes required for DNA synthesis,
Gemcitabine has been studied extensively as a single agent in
previously untreated NSCLC in Europe, Japan, South Africa, and
Canada. In several studies involving nearly 600 evaluable patients,
responses ranged from 20% to 27%, said Dr. Sandler assistant professor
of hematology/oncology, and medical director, Thoracic Oncology
Program, Indiana University School of Medicine, Indianapolis.
Phase I/II studies have established a maximally tolerated gemcitabine
dose of 1,250 mg/m²/wk, with myelosuppression and thrombocytopenia
the dose-limiting toxicities. Nonhematologic toxicities include
reversible hepatotoxicity, proteinuria, mild skin rash with or
without pruritus, and nausea with vomiting.
Dr. Sandler reported on five recent phase II studies of gemcitabine
in combination with cisplatin (Platinol). All included a regimen
of weekly gemcitabine for 3 weeks, with 1 week off; cisplatin
was given in varying doses.
In patients with previously untreated stage III NSCLC, response
rates ranged from 31% to 55%, and median survival rates were as
high as 9.9 months. The most favorable response was seen in an
Italian study that administered gemcitabine weekly, 1,000 mg/m²
on days 1, 8, and 15, with cisplatin 100 mg/m² on day 2.
With a median follow-up of 11 months, median survival has not
yet been reached for that regimen.
Studies are ongoing for gemcitabine in combination with carboplatin
(Paraplatin) and ifosfamide (Ifex), with no response results yet
reported, he said.