A RANDOMIZED TRIAL OF MACC CHEMOTHERAPY WITH OR WITHOUT LONIDAMINE INADVANCED NONSMALL CELL LUNG-CANCER

Combination chemotherapy with anti-proliferative agents is the usual t reatment for patients with advanced nonsmall cell lung cancer (NSCLC), good performance status and no major clinical contraindications. Loni damine (LND), a new drug with an innovative mechanism of action, might potentiate anti-cancer activity of conventional cytotoxic drugs, with no increase of specific toxicity. Following a pilot study of feasibil ity, we now report the results of a randomised trial evaluating MACC c hemotherapy, as originally described, versus the same regimen + LND. 1 51 patients with advanced NSCLC were assigned at random to the two tre atment arms. LND 150 mg was given orally three times daily. Treatment was continued until progression of disease, unacceptable toxicity or r efusal by the patient (median number of cycles of MACC, three for both arms; median duration of LND administration, 8 weeks in the arm conce rned). Actual dose intensities (DI) of MACC and LND were, respectively , 100 and 83% of those intended (median values). There was a negative correlation between duration of chemotherapy and the DI of MACC reache d in each patient, but no correlation between the duration of treatmen t with LND and its DI. DIs of LND and MACC were not correlated with ea ch other. In all, 15 objective responses (one complete and four partia l responses in the MACC group, 10 partial responses in patients on MAC C + LND) were observed. Median progression-free survivals were 20 week s (confidence interval, CI 14-22) for the group on LND and 17 weeks (C I 12-17) for the control group (non-significant difference). Median ov erall survivals were, respectively, 30 weeks (CI 23-40) and 27 weeks ( CI 22-34), P = non-significant. Toxicity was as expected by the use of MACC, and similar in both arms, except for more severe anaemia and ga stric toxicity in the group on MACC + LND. Other uncommon side-effects , seen only in this latter group, were mild to moderate and reversible and included myalgia, asthenia, testicle pain, headache, visual troub les, incubi and dizziness. Subjective tolerance to the treatment, and perception of physical and psychological well-being were rated similar ly by patients of both groups. MACC plus LND is a moderately active re gimen in advanced NSCLC, with a foreseeable and reversible toxicity of low-medium grade. Potential enhancements of anti-tumour efficacy of c hemotherapy, and possible host survival benefits derived from the use of LND are not substantiated by the results of this trial.