GROSSHANSDORF, Germany—Initial efficacy results of a randomized phase III trial of previously untreated small-cell lung cancer (SCLC) show that paclitaxel(Drug information on paclitaxel) (Taxol)/etoposide/carboplatin (TEC) and carboplatin(Drug information on carboplatin)/etoposide/vincristine (CEV) are both well tolerated with similar response rates. The findings were presented at the 36th Annual Meeting of the American Society of Clinical Oncology (ASCO).
The study is the first large phase III trial to compare the efficacy and toxicity of the newer TEC regimen to that of CEV, a widely used standard regimen for SCLC in Germany. The interim results were presented by Ulrich Gatzemeier of Grosshansdorf Hospital, Germany.
Both regimens have a balanced toxicity profile. The TEC arm had a slight advantage in that thrombocytopenia and anemia were lower, and polyneuropathy was less frequent. The researchers concluded that TEC is a safe and effective regimen in the treatment of SCLC, Dr. Gatzemeier said.
No survival data were presented at ASCO. Although the trial began enrollment of 615 patients in February 1998 and finished in December 1999, two months ahead of schedule, response data were available for only the first 373 patients.
“I apologize for not presenting survival data,” Dr. Gatzemeier said. “We decided to do no interim analysis at this point. We have to wait for the final analysis at the end of the year. The last patients are still on treatment.”
Toxicity data were available for the 437 patients who have completed therapy.
The study showed a 92.8% response rate for the TEC arm and an 87.0% response for the CEV arm. “It might be the fact that we had a few more primary progressive disease patients in the standard arm. Thirteen patients had primary progressive disease in the standard arm in comparison to only three patients in the TEC arm,” Dr. Gatzemeier said.
The study enrolled 615 patients with previously untreated SCLC who were stratified by disease stage (I-IIIB vs IV). “Patient characteristics were well balanced between both groups,” Dr. Gatzemeier said. Among the enrolled patients, 93% had ECOG performance status 0-1, and 7% had ECOG performance status 2.
Of the patients enrolled, 315 had extensive disease, and 300 had limited disease. The TEC arm enrolled 306 patients, and the CEV arm enrolled 309.
The primary objective was median survival. Secondary objectives included time to progression, response rate, toxicity, and quality of life.
Patients in the TEC arm received paclitaxel 175 mg/m² IV (3 h) on day 4, etoposide(Drug information on etoposide) 125 mg/m² IV on days 1 to 3, and carboplatin AUC 5 IV (30 min) on day 4. Treatment was repeated every 3 weeks for a maximum of six cycles.
Patients in the CEV arm received carboplatin AUC 5 IV (30 min) on day 1, etoposide 159 mg/m² IV on days 1 to 3, and vincristine 2 mg IV on days 1 and 8. Treatment was repeated every 3 weeks for a maximum of six cycles.
Patients with stage IV disease received a lower dose of etoposide for safety reasons. Those in the TEC arm received 102.2 mg/m², and patients in the CEV arm received 125 mg/m².
Dr. Guiseppe Giaccone, of the Free University Hospital, Amsterdam, The Netherlands, who served as the session discussant, questioned the differing doses of etoposide given.
The higher myeolotoxicity observed in the CEV arm compared with the TEC arm may be due to the variation in the etoposide doses, he said. “I noticed in this study that the doses of etoposide applied were different based not only on the stage of the disease but also on the arm.”
Hematologic toxicities were as follows: Common Toxicity Criteria grade 3-4 neutropenia occurred in 45.8% of the patients in the TEC arm vs 47.9% of the patients in the CEV arm. Grade 3-4 febrile neutropenia occurred in 2.9% of the patients in the TEC arm vs 4.0% of patients in the CEV arm. Grade 3-4 anemia occurred in 1.8% of the patients in the TEC arm vs 5.8% of patients in the CEV arm.
Nonhematologic toxicities included grade 3-4 polyneuropathy, which occurred in 0.7% of patients in the TEC arm vs 2.2% patients in the CEV arm. Pain was reported by 0.7% of the patients in the TEC arm vs 1.4% of patients in the CEV arm. Nausea occurred in 0.9% of patients in the TEC arm vs 0.7% in the CEV arm.
“It’s disappointing that the progression and survival data were not ready for presentation,” said Corey Langer, MD, co-chair of the ASCO session. “It was a very reasonable, well-powered, trial.”
