Are ‘Platins’ on the Way Out in Regimens for NSCLC?

Seeking effective drugs for advanced non–small-cell lung cancer (NSCLC), researchers are trying ever more creative combinations, and at the 35th annual meeting of the American Society of Clinical Oncology (ASCO), some investigators suggested that platinums may be “on the way out” as pivotal components of regimens for the disease.

Paclitaxel/Carboplatin Equal toVinorelbine/Cisplatin in SWOG 9509

The standard therapy for patients with advanced NSCLC in Southwest Oncology Group (SWOG) trials has been the VC regimen (vinorelbine [Navelbine] plus cisplatin [Platinol]). However, because of the results of the SWOG 9509 phase III study, that combination is likely to be replaced by PC (paclitaxel [Taxol] and carboplatin [Paraplatin]), said Karen Kelly, MD of the SWOG.

Vinorelbine plus cisplatin and paclitaxel plus carboplatin were equally effective in treating patients with untreated NSCLC, but PC may be preferred because of a “favorable toxicity profile and better tolerability and compliance,” said Dr. Kelly. The trial included 202 patients treated with VC and 208 treated with PC. Eligibility required measurable or evaluable disease, a performance status of 0 or 1, adequate organ function, and no prior chemotherapy.

Hematologic toxicity was significantly worse in the VC-treated patients (Table 1). The main toxicity problem in those given PC was peripheral neuropathy. Significantly more patients were able to complete therapy in the PC arm than in the VC arm (26% vs 16%; P = .015) Response rates were essentially the same for both regimens. There were 0 complete responses and 56 (28%) partial responses with VC vs 1 complete response and 51 (25%) partial responses with PC. Progression-free survival was about 4 months with either regimen, and overall survival, about 8 months.

The SWOG investigators also performed a pharmacoeconomic analysis that included 182 patients on VC and 180 patients on PC. Dr. Kelly reported that the analysis showed drug costs for VC were $4,116 vs $19,895 for PC, and total treatment costs for VC were $17,876 vs $34,393 for PC. The question of whether PC should be considered standard therapy, given its equal efficacy and lower toxicity, is being considered in the design of future SWOG studies, said Dr. Kelly. However, she emphasized that the most important benefit of this regimen is that its low toxicity “may allow us to add a third agent, as long as it does not cause neuropathy.”

“I think we are moving away from the platinums altogether,” she added.

Docetaxel/Cisplatin vs Docetaxel/Gemcitabine: Comparable Activity?

Vassilios Georgoulias, MD, of University General Hospital, Iraklion, Crete, Greece also raised the question of “whether platinum compounds should be a major constituent of therapy for non-small-cell lung cancer,” based on preliminary data from the Greek Cooperative Group for Lung Cancer. Docetaxel (Taxotere)/cisplatin and docetaxel/gemcitabine (Gemzar) showed similar efficacy in previously untreated patients with advanced NSCLC in early reports from that trial.

This phase II, randomized trial was conducted to compare the efficacy and toxicity of these regimens. The trial will accrue a total of 412 patients. Dr. Georgoulias reported preliminary data on 347 patients with stage IIIB or IV NSCLC. Patients were randomized to receive either docetaxel (100 mg/m² on day 1) and cisplatin (80 mg/m² on day 2) or gemcitabine (1,100 mg/m² on days 1 and 8) and docetaxel (100 mg/m² on day 8). Patients on both arms received recombinant human granulocyte colony-stimulating factor (Neupogen; 150 mg/m² subcutaneously). Cycles were repeated every 3 weeks.

Dr. Georgoulias said that there were no significant differences in time to progression, median survival, or 1-year survival between the two regimens (Table 2). There were also no differences in grade 3/4 anemia or throm-bocytopenia. However, grade 3 neutropenia was significantly higher with docetaxel/cisplatin than with docetaxel/gemcitabine (34% vs 20%; P = .03) as was nausea/vomiting (11% vs 2%; P = .005). Fluid retention (21% vs 12%; P = .005) and febrile neutropenia/infection (29% vs 17%; P = .004) were more common with docetaxel/gemcitabine.

Another advantage of the docetaxel/gemcitabine regimen is that it can be given as outpatient treatment, while treatment with docetaxel/cisplatin requires hospitalization. “These preliminary results seem to indicate that the docetaxel/cisplatin and the docetaxel/gemcitabine regimens have a comparable activity and toxicity profile in patients with advanced non-small-cell lung cancer,” said Dr. Georgoulias.

In discussing this study, Thomas Lynch, MD, of Massachusetts General Hospital, Boston, suggested that the 1-year survival rates in this study were higher than previously reported in SWOG studies and “may reflect the relative numbers of stage III and stage IV patients we see in the US vs those in European trials.”