NANTES, France --The seventh trial of adjuvant Navelbine (vinorelbine)-Platinol (cisplatin) tips the balance toward improved survival in patients with stage IB to IIIA non-small-cell lung cancer (NSCLC).
NANTES, France, Aug. 18 -- Adjuvant Navelbine (vinorelbine)-Platinol (cisplatin) improved overall survival in patients with stage IB to IIIA non-small cell lung cancer (NSCLC), according to results of a multicenter trial.
The benefit was mainly driven by patients with stage II and IIIa disease, Jean-Yves Douillard, M.D., and the ANITA (Adjuvant Navelbine International Trialist Association) investigators reported online Aug. 16 in The Lancet Oncology.
The adjusted mortality risk for the adjuvant chemotherapy patients was significantly lower (hazard ratio 0.80 [95% C.I. 0.66-0.96] P=0.017) than controls, the ANITA trialists reported. Overall survival was 8.6% better at five years, which was durable at seven years.
Three previous trials have shown a survival benefit for the Navelbine-Platinol doublet and three demonstrated no increased benefit. The ANITA results, the seventh trial, tip the balance toward a survival benefit.
From December 1994 to December 2000, 840 patients from 101 centers in 14 countries, including the United States, were randomized to observation after surgery alone or to surgery plus four cycles of Navelbine (30 mg/m2 ) plus Platinol (100 mg/m2 ).
The authors cautioned that "although this regimen was feasible, 2% of patients died from toxic effects," a higher rate than reported in similar trials.
They said the toxicity probably reflected the relatively high doses of Navelbine and Platinol used in the trial and they suggest that these doses might need to be altered to a less toxic regimen of 50 mg/m2 of Platinol on days one and eight, and 25 mg/m2 of Navelbine per week, or other less-toxic combinations.
The most frequent grade 3-4 toxicities were neutropenia, anemia, and febrile neutropenia. Other side-effects included asthenia, nausea, vomiting, anorexia, and infection.
The trial was not designed to assess the benefit of postoperative radiotherapy, although eighty-eight of the chemotherapy patients and 144 of the controls received radiotherapy according to the policy of participating centers, so observations about the efficacy of radiotherapy are tenuous. Nonetheless, "the descriptive analysis showed that radiotherapy could benefit patients with N2 status and could be harmful when combined with chemotherapy in patients with N1 status."
The median age of patients was 59 and more than 85% were men. Thirty-nine percent of patients had postoperative stage III disease, 24% had stage II disease, and 36% had stage I disease.
Forty-four percent of the chemotherapy patients and 43% of the control patients had no nodal involvement. There was spread to one node in 26% of the chemotherapy patients and 31% of controls. Two-node disease was identified in 29% of the chemotherapy patients and 24% of controls. Nodal status was missing in 1% of each treatment group.
Roughly 60% of tumors were squamous cell carcinoma and 40% were non-squamous-cell carcinoma.
Ninety percent of the chemotherapy patients received Navelbine and concurrent Platinol. Half of the patients completed the planned four cycles of chemotherapy.
To identify subsets of patients who could have greater benefit from adjuvant chemotherapy, genetic assessment of the patients in this trial is under way.
The study was supported by a grant from Institut de Recherche Pierre Fabre.