A DOUBLE-BLIND RANDOMIZED STUDY OF ORAL CLODRONATE IN THE TREATMENT OF BONE METASTASES FROM TUMORS POORLY RESPONSIVE TO CHEMOTHERAPY

Bisphosphonates are used in oncology as a means of decreasing complica tions due to bone metastases, in association with anticancer treatment , especially in patients with breast cancer, prostate cancer and myelo ma, Little is known about the effects of bisphosphonates on bone metas tases from other tumors and in particular from tumors for which no eff ective treatment is available. We conducted a:randomized, double-blind placebo-controlled trial of oral clodronate in patients with bone met astases from turners poorly responsive to chemotherapy, with the aims of evaluating the effects of this drug on symptoms control and bone me tastases evolution. Sixty-six patients with poorly responsive tumors s uch as non-small cell lung cancer (NSCLC), bladder cancer, gastrointes tinal cancers, kidney cancer, melanoma and metastatic carcinoma of unk nown origin entered the study. Patients were randomized to receive eit her clodronate 1,600 mg:day for one year or identical placebo-containi ng tablets. Various parameters such as Karnofsky performance status, p ain score (measured by a visual-analogue scale) and analgesics require ment were recorded at monthly intervals. Of the 66 patients enrolled, 9 were observed for one month or less; 7 were followed for two months; only 50 patients were followed for more than 2 months and could be ad equately evaluated. At 3 months both clodronate and placebo-treated pa tients had a decrease in Karnofsky performance status, with the decrea se being more evident in the placebo group. Mean pain scores showed an increase of pain in patients receiving placebo and a decrease of pain in patients receiving clodronate, although the difference failed to b e statistically significant. Analgesics requirement increased in both groups, but significantly more in patients receiving placebo (p=0.042) , in whom increase in opioid requirements was particularly evident. To xicity was low, with occasional gastroenteric discomfort in both group s. The main problem of this study was the difficulty in recruiting an adequate number of patients and following them for a sufficient period of time: general conditions rapidly deteriorated in many patients, an d approximately 25% of the 66 enrolled were not considered evaluable; :Few patients survived for the length of the study, one year. This mig ht partly account for the lack of significance of some of the paramete rs under study. With these limits, oral clodronate demonstrated some e fficacy in symptom control and in I-educing the need for analgesics.