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).
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."