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 (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 (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-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 in NSCLC
treatment (Gralla R et al: Annals of Oncology 10(suppl
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 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
New therapeutic options like angiogenesis inhibitors or
matrix metalloproteinase (MMP) inhibitors must be examined, Dr.