Gemcitabine/Cisplatin Superior to Cisplatin Alone in Advanced NSCLC

INDIANAPOLIS--Patients with advanced non-small cell lung cancer (NSCLC) have higher response rates, longer time to progression, and better overall survival with gemcitabine (Gemzar) plus cisplatin (Platinol) than with cis-platin alone, according to data from a multicenter, randomized, phase III study presented at the annual ASCO meeting.

Alan B. Sandler, MD, of the Indiana University School of Medicine, reported on behalf of the Hoosier Oncology Group and other research centers in the United States, Canada, and Europe.

The control arm was cisplatin, 100 mg/m² every 4 weeks. The experimental arm used the same dose of cisplatin with gemcitabine, 1 g/m² given on days 1, 8, and 15 every 4 weeks. Patients received a maximum of 6 cycles of therapy, Dr. Sandler said. The principal endpoint was overall survival.

From August 1995 through February 1997, the study accrued 522 patients. Dr. Sandler reported on the interim analysis of the first 309 patients. Overall survival data were presented for all 522 patients.

Eligibility criteria included histologically or cytologically confirmed measurable or evaluable stage IIIa, IIIb, or IV NSCLC. Patients had received no prior chemotherapy. They were stratified by disease stage (III vs IV) and performance status.

The response rate was 32% for the combination of gemcitabine and cisplatin vs 10% for cisplatin alone (P < .0001). "There was a trend in favor of a longer median duration of response for the combination (6.9 months vs 4.2 months for cisplatin alone), but it did not reach statistical significance," Dr. Sandler said. Patients on gemcitabine plus cisplatin had a significantly increased median time to progressive disease--5.8 months vs 3.7 for cisplatin alone (P = .0001).

Median Survival

In the final analysis of all 522 eligible patients on study, median survival was 9.1 months on the gemcitabine/cisplatin arm vs 7.6 months for cisplatin alone (P = .012). The probability of 1-year survival was 39% for gemcitabine plus cisplatin vs 28% for cisplatin alone.

"Not surprisingly, there was an increase in hematologic toxicity seen in the combination arm," Dr. Sandler said. About one-third (34%) of patients required packed red blood cell transfusions on the combination arm vs 10% on the cisplatin alone arm.

There was an increase in the need for red blood cell transfusion with increasing cycles of therapy. "It should be noted that the median number of cycles received was 4 on the combination arm vs 2 on the control arm," he said.

On the combination arm, 22% of patients required platelet transfusions vs none on the cisplatin arm. "However, there were no serious hemorrhagic events noted on either arm," Dr. Sandler pointed out. The incidence of neutropenic fever was low and similar between the two arms. There were no toxic deaths in either arm. Nonhematologic toxicity was mild.

"The combination of gemcitabine plus cisplatin is superior to cisplatin alone in patients with advanced or metastatic non-small-cell lung cancer with respect to response rate, time to progression, and overall survival," Dr. Sandler concluded.

Bone marrow suppression was more pronounced with the combination of gemcitabine plus cisplatin than with cisplatin alone, although without serious sequelae, he said. Nonhematologic toxicities occurred at approximately the same frequency in both of the treatment arms.

In her discussion of the study, Frances Shepherd, MD, said that "these results suggest that gemcitabine and cisplatin produce results that are similar to the taxane plus cisplatin or carboplatin combinations."