HAMBURG, GermanyThe overall results of the treatment of advanced nonsmall-cell lung cancer are unsatisfactory, Ulrich Gatzemeier, MD, said in an overview of recent German trials he presented at the 9th World Conference on Lung Cancer. Dr. Gatzemeier is head of the Department of Thoracic Oncology with Hospital Grosshansdorf, Hamburg, Germany.
Modern chemotherapy options for nonsmall-cell lung cancer in that country include gemcitabine(Drug information on gemcitabine) (Gemzar), vinorelbine (Navelbine), and the taxanes in combinations that include a platinum compound. According to 1999 data presented at the meeting, some of the most popular first-line therapies for nonsmall-cell lung cancer include gemcitabine/cisplatin (Platinol) (13% of cases), vinorelbine/cisplatin (13%), and etoposide(Drug information on etoposide) (VePesid)/cisplatin (9%). For second-line therapy, single-agent gemcitabine is the most commonly used therapy (22% of cases), followed by vinorelbine (14%), and gemcitabine/cisplatin (11%).
Seeking Non-platinum Regimens
A popular investigational approach these days is to seek out non-platinum-containing regimens that may have efficacy. One recently conducted phase- II investigation by Dr. Gatzemeier and colleagues, reported in another session at the World Conference, looked at the combination of gemcitabine and mitomycin(Drug information on mitomycin)-C (Mutamycin). Both of these drugs, which have different mechanisms of action, are active as single agents in NSCLC. In addition, both have been evaluated, with promising results, as alternative partners with cisplatin(Drug information on cisplatin) in NSCLC treatment (Gralla R et al: Annals of Oncology 10(suppl 5):S47-S51, 1999).
Using a dosing schedule shown safe and feasible in a phase I trial (gemcitabine 1,000 mg/m² per day on day 1, 8, and 15, plus 8 mg/m² mitomycin on day 1 of the cycle), Dr. Gatzemeier and colleagues have treated 32 patients with histologically proven stage IIIB-IV NSCLC. Dexamethasone(Drug information on dexamethasone) was also administered due to pulmonary toxicity observed in the earlier investigation.
Of 26 patients available for evaluation, the overall response rate was 41%, with median time to progression of 21 weeks. The most common serious toxicities were hematologic, including grade 3/4 thrombocytopenia in 31%, grade 3/4 neutropenia in 25%, and grade 3/4 anemia in 3%.
No serious episodes of febrile neutropenia occurred. Nonhematologic toxicities were rare and included edema and dyspnea. Half the patients had grade 1/2 pulmonary toxicities. There were no serious gastrointestinal adverse effects. The toxicity is manageable, and subjective tolerance is excellent, Dr. Gatzemeier said.
Although the combination regimen, which can be administered in the outpatient setting, demonstrated activity against NSCLC, confirmatory studies are needed, Dr. Gatzemeier noted. He added that German researchers are hoping to expand options beyond the traditional.
New therapeutic options like angiogenesis inhibitors or matrix metalloproteinase (MMP) inhibitors must be examined, Dr. Gatzemeier said.