LINKOPING, Sweden-Swedish researchers found that gemcitabine (Gemzar) plus carboplatin (Paraplatin) improved response rates and survival in patients with advanced non-small-cell lung cancer during a phase III trial, according to a
LINKOPING, SwedenSwedish researchers found that gemcitabine (Gemzar) plus carboplatin (Paraplatin) improved response rates and survival in patients with advanced non-small-cell lung cancer during a phase III trial, according to a presentation by C. Sederholm, MD, on behalf of the Swedish Lung Cancer Study Group. Dr. Sederholm is with the department of pulmonary medicine at University Hospital, Linkoping (ASCO abstract 1162).
"Combination gemcitabine plus carboplatin increased survival without complicating toxicities or detriment to quality of life compared with gemcitabine alone," Dr. Sederholm said.
Researchers enrolled 334 patients at 17 centers from October 1998 through January 2001. Eligibility criteria included histologically/cytologically confirmed stage IIIB or IV disease and performance status of 0 to 2. There was no upper age limit. Patients with known central nervous system metastatic disease were excluded.
The primary study endpoint was survival. Secondary endpoints were quality of life, safety, time to progression, and response rate.
Patients were randomized into two treatment arms. In the first, 170 patients received an intravenous infusion of gemcitabine, 1,250 mg/m², on days 1 and 8, every 21 days. The 164 patients in the second arm were given the same regimen of gemcitabine plus carboplatin, AUC of 5, on day 1, every 21 days.
A maximum of six cycles were planned. Doses were adjusted downward according to hematologic toxicity. The median number of cycles given was five in the gemcitabine arm and six in the combination arm. The dose intensity was excellent in both treatment groups.
Patients were followed up every 2 months for a year and every 3 months after the first year until progressive disease or death. Second-line treatments were given. A crossover to second-line treatment with a platinum regimen was not allowed.
The treatment arms were well balanced, with no significant differences in prognostic factors. The median age was 67, with 40% of the patients being age 70 or older. The most common histology was adenocarcinoma (49% in each arm), followed by squamous cell carcinoma. More than a third of the patients had more than 5% weight loss at baseline, with a slight predominance in the gemcitabine arm (35% vs 29%). Eighty-five percent of the study population had a performance status of 0 to 1. Eight patients never received treatment for various reasons.
"The hematologic toxicity, grade 3 and 4, was as expected, definitely more pronounced in the combination arm, but there were no treatment-related deaths in either arm," Dr. Sederholm said. "Five percent of the patients in the combination arm experienced grade 3 hematologic toxicity, compared to less than 2% in the single-agent arm."
The most common toxicities were anemia, leukopenia, and thrombocytopenia. Chemotherapy-related infections were rare, with one in each arm. Thrombocytopenia, observed in a high proportion of patients in the combination arm, was short-lived, centering around day 15 and without clinical implications in the vast majority of patients. No major bleeding was reported. Nonhematologic toxicities were mild, with no significant differences between arms.
Combination Highly Beneficial
"The objective response rate in the 291 evaluable patients was highly significant in favor of the combination arm30%, with two patients achieving a complete response, vs 12% in the gemcitabine arm," Dr. Sederholm said.
Time to progression in the intention-to-treat population was 4 to 6 months in the combination group, and the 1-year disease-free rate was 4% to 12%.
Second-line treatment was evenly distributed. Eight percent of the patients in the gemcitabine arm later crossed over to a platinum regimen against protocol.
Overall survival in the intention-to-treat analysis found 15% of patients still alive8% in the gemcitabine arm and 27% in the gemcitabine-plus-carboplatin combination arm. The investigators found an overall survival benefit in favor of the gemcitabine/carboplatin combination.
"Overall survival was significantly superior in the combination group," Dr. Sederholm said. "The higher response rate, time to progression, and improved survival supports the use of these combinations even in elderly patients with good performance status."