In subgroup analyses, adjuvant cisplatin-vinorelbine provides a superior survival benefit and can be recommended in completely resected stages II and III non-small cell lung cancer.
To determine whether hypoxia has a direct influence on the central command independently of the working muscles, 16 subjects performed intermittent isometric unilateral knee extensions until exhaustion either in normobaric hypoxia (inspired O(2) fraction=0.11, arterial oxygen saturation approximately 84%) or in normoxia while the knee extensor muscles were exposed to circulatory occlusion with a 250 mmHg cuff. Among the subjects, 11 also performed the tests in hypoxia and normoxia without occlusion. Single electrical stimulations were regularly delivered to the femoral nerve to measure the changes in the knee extensor peak twitch force. With the cuff, the average slope of decrease in peak twitch did not depend on the inspired oxygen fraction. Performance was slightly but significantly lower during hypoxia than in normoxia (8.2+/-2.6 vs 9.4+/-3.1 repetitions, P<0.05) with the cuff on. The number of repetitions was much higher during hypoxia with maintaining leg blood flow (15.6+/-4.5 repetitions) than with circulatory occlusion in normoxia. In conclusion, this study showed that a direct effect of hypoxia in reducing the motor drive to the working muscles exists but this effect is moderate.
The efficacy and safety of the alternating vinorelbine schedule (i.v. on day 1, oral on days 8, 15 and 22) in combination with cisplatin in advanced NSCLC are similar to those of the standard regimen using exclusively i.v. vinorelbine, whereas ease of administration and patient comfort may favor the novel approach.
The different schedules of vinorelbine in the two arms led to a greater survival in the NP arm without impairing the tolerance profile, although this is not statistically significant. This confirms that the two-drug combination NP is a reference treatment for metastatic NSCLC. The role of three-drug combinations remains questionable in this subset of patients.
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