Alternating Docetaxel With Cisplatin/Vinorelbine Less Toxic in NSCLC

ASCO--Cycling docetaxel (Taxo-tere) treatments with cisplatin(Platinol) and vinorelbine (Navelbine) achieves better responserates in non-small-cell lung cancer (NSCLC) patients than canbe expected from any of the components used alone or in traditionalcombination, according to the multicenter pilot study presentedby Jean Viallet, MD, at a pos-ter session of the American Societyof Clinical Oncology (ASCO) meeting in Philadelphia.

The goal of the alternating drug regimen in the phase II trialwas to capitalize on the efficacy of each of the agents whileavoiding any cumulative toxicity. "These three agents arearguably the three most active individual agents in the treatmentof NSCLC," said Dr. Viallet, director of the Oncology Centerat the Hospital Notre-Dame, Montreal.

Unfortunately, prior attempts at devising regimens pairing theagents have not been well tolerated.

Effects of Same Day Dosing

"When you try to give docetaxel with cisplatin or docetaxelwith vinorelbine on the same day, the impact on the white bloodcell count is such that a substantial fraction of patients areexposed to the risk of febrile neutropenia and infectious complications,"Dr. Viallet told Oncology News International in an interview.

Traditionally, clinicians have reduced doses in an effort to compensatefor this effect--with the result that efficacy is lost, Dr. Vialletnoted. As an alternative strategy, Dr. Viallet and his colleaguescycled the treatments, giving docetaxel first and then, 3 weekslater, administering the cisplatin with vinorelbine.

Unlike the earlier strategy, which provided small, suboptimaldoses to reduce the chance of cumulative side effects, here eachpatient received a full dose of each drug. "This way we wouldavoid the potential cumulative toxicity, while hopefully obtainingefficacious and perhaps even additive activity," Dr. Vialletsaid.

To determine efficacy, 45 patients with measurable advanced NSCLCwere enrolled in eight Canadian centers over a period of 9 months.In a 6-week cycle, patients received 100 mg/m² of docetaxeladministered on day one, 100 mg/m² of cisplatin on day 21,and 30 mg/m² of vinorelbine on days 21, 28, and 35.

Preliminary results were promising, Dr. Viallet said. Tumor shrinkagewas significant in 19 of 41 evaluable patients (46%). Historicalresponse rates for cis-platin and vinorelbine in combination havebeen about 29%, and for docetaxel alone, between 28% and 30%,he noted.

Cumulative Side Effects Reduced

Side effects observed were those well known and associated witheach of the agents alone, Dr. Viallet said. There was no evidencefor potentiation of side effects. In fact, because the dose intensityof the individual components of the regimen were diluted by half,the cumulative side effects of the drugs appeared to be actuallyreduced, he said.

Dr. Viallet expressed satisfaction overall with the results andnoted that he plans to continue to test the regimen both in NSCLCand other cancers, particularly breast cancer. "I think thatif we can learn how to use this approach in earlier stages ofthe disease, we might actually be able to show that it improvessurvival," he said.