NEW HAVEN, ConnTopoisomerase I inhibitors in combinations not
based on platinum have shown significant activity in
nonsmall-cell lung cancer (NSCLC), John R. Murren, MD,
reported. These combinations include such drugs as taxanes,
gemcitabine (Gemzar), and vinorelbine (Navelbine). Dr. Murren,
Associate Professor of Medicine at Yale University School of
Medicine, New Haven, Connecticut, reviewed research on these regimens
at a clinical investigators workshop sponsored by the
University of Texas M. D. Anderson Cancer Center and Pharmacia
One trial of interest is a phase II study of paclitaxel (Taxol) and
irinotecan (Camptosar) in patients who have stage IV NSCLC or
malignant pleural effusions and have not been previously treated.
Paclitaxel 75 mg/m² is infused over 1 hour, followed immediately
by irinotecan 50 mg/m² as a 30-minute infusion. The planned
treatment cycle consists of 2 weeks on, 1 week off therapy, with
irinotecan doses escalated to 60 mg/m² if toxicity permits.
Thirty-one cycles of treatment have been delivered so far, and Dr.
Murren said that 2 patients have been escalated to the higher
irinotecan dose. Delivered dose intensity has been 97% of planned.
Responses and Toxicities
Six of seven patients are evaluable for response, including one with
a partial response that has lasted for more than 24 weeks, three with
stable disease for 17-25 weeks, and one with disease progression.
There was one incident of grade 3 diarrhea but no other grade 3
toxicities. Neurotoxicity occurred at grade 2 in one patient and
grade 1 in three patients.
Paclitaxel 75 mg/m² followed by irinotecan 50 mg/m²
on a weekly schedule is very well tolerated in advanced NSCLC,
Dr. Murren said. Neutropenia is the dose-limiting
toxicity. This study found no drug-drug interaction. Among two
other studies reported, one also found no drug-drug interaction and
the other, reported at the American Society of Clinical Oncology
(ASCO) meeting this year, suggested that paclitaxel alters the
pharmokinetics of irinotecan. Further evaluation of this
regimen is warranted, Dr. Murren said.
Irinotecan has also been tested in combination with docetaxel
(Taxotere) in NSCLC. Dr. Murren said that the maximum tolerated dose
of docetaxel was 35 mg/m² combined with irinotecan 50 mg/m²
given weekly for 4 weeks followed by a 2-week rest. We are
currently treating patients on a 2 week on, 1 week off, schedule
(similar to the schedule being used with irinotecan and paclitaxel)
and have been able to escalate the dose of irinotecan to 60 mg/m²
, Dr. Murren told ONI.