Treatment of multiple myeloma according to the extension of the disease: a prospective, randomised study comparing a less with a more aggressive cystostatic policy. Cooperative Group of Study and Treatment of Multiple Myeloma.

The purpose of the study was to ascertain whether the prognostic significance of staging in multiple myeloma (MM) is influenced by the aggressiveness of effective induction treatment and/or by continuing or discontinuing maintenance chemotherapy. Patients with untreated stage I MM (defined according to Durie and Salmon) were randomised between being followed without cytostatics until the disease progressed and receiving six courses of melphalan and prednisone (MP-P) just after diagnosis; stage II patients were uniformly treated with MPH-P and stage III patients were randomised between MPH-P and four courses of combination chemotherapy with Peptichemio, vincristine and prednisone (PTC-VCR-P). Within each stage, responsive patients were randomised between receiving additional therapy only until maximal tumour reduction was reached (plateau phase) and continuing induction therapy indefinitely until relapse. With resistant, progressive or relapsing disease, patients originally treated with MPH-P for induction received combination chemotherapy and vice versa. The overall first response rate was 43.8% (42.2% in 206 stage I, II and III patients treated with MPH-P and 48.0% in 75 stage III patients treated with combination chemotherapy, P = NS). Combination chemotherapy was more myelotoxic than MPH-P and, in particular, caused more non-haematological side-effects. Both the less and the more aggressive induction policies gave the same disease control. Progression of disease was statistically similar in stage I patients who were initially left untreated and in t hose who received MPH-P just after diagnosis; median duration of first response was similar in stage III patients receiving MPH-P and in those on combination chemotherapy. In all stages, discontinuing or continuing maintenance did not alter the median duration of first response. The overall second response rate was 28.5% (34.0% to MPH-P and 25.3% to combination chemotherapy, P = NS). Median survival was greater than 78 months in stage I, was 46.3 months in stage II and was 24.3 months in stage III patients, still independent of both induction and post-induction policies. In MM, the significance of staging for survival is independent of both the aggressiveness of induction and of continuing or discontinuing maintenance chemotherapy after the maximal tumor reduction has been achieved. Both MPH-P and and the association of PTC, VCR and P are effective in inducing first response and also second response in patients failing on the alternative regimen, but PTC-VCR-P causes more side effects. Thus, the overwhelming majority of patients with MM can safely be given MPH-P as first therapy, and this treatment may be delayed in early diseases.

A prospective, controlled, nonrandomized study on prophylactic parenteral dichloromethylene bisphosphonate (clodronate) in multiple-myeloma.

Bone resorption by osteoclasts causes neoplastic bone disease, which is a significant cause of death in multiple myeloma (MM). Counteracting bone resorption with prophylactic bisphosphonates has delayed bane disease, and this is expected to improve survival. Between January, 1987 and March, 1990, 341 evaluable previously untreated, consecutive patients with MM entered a prospective, multicenter study in which cytostatic therapy was randomized. The first 148 patients recruited were not planned for prophylaxis and the following 193 were scheduled to receive parenteral, prophylactic clodronate. Clodronate was administered at a dose of 600-1000 mg/4-6 weeks and was started at diagnosis and continued throughout survival time. Data on clodronate prophylaxis were evaluated on both an intention-to-treat and a compliance analysis basis. The rate of response and the duration of response were independent of clodronate prophylaxis. Progression of skeletal disease occurred less often in patients who received the drug than in those who were not given prophylaxis (50.5 vs 34.8%; p<.02 by compliance analysis). Survival was longer for patients on clodronate prophylaxis than for those who were not planned for (p<.02 by intention to-treat-analysis) or for those who did not receive clodronate prophylaxis (p<.009 by compliance analysis). Local pain associated with i.m. administration was the only significant side effect of clodronate. Parenteral clodronate prophylaxis prolongs survival in MM, probably because it allows better control of bone disease and reduces deaths related to it.

[Randomized study of the antiemetic efficacy of alizapride versus alizapride + dexamethasone]. / Studio randomizzato sull'efficacia antiemetica dell'alizapride versus alizapride + desametasone.

We made a study on patients suffering from neoplasias treated with cisplatinum to compare antiemetic efficacy of alizapride or associated to dexamethasone. We divided patients in two groups. We somministred alizapride alone to the first group and alizapride plus dexamethasone to the second one. We evaluated presence or absence of emesis, its intensity and eventual tossic effects due to the drugs through an autocompilative questionnaire given to the patients. Our results didn't show important statistical differences between the two groups, though association with dexamethasone gets better emesis control. Alizapride anyway, didn't present important collateral effects, particularly extrapyramidal ones.