Oral clodronate and reduction in loss of bone mineral density in women with operable primary breast cancer.

BACKGROUND: Women with primary breast cancer who receive systemic therapy may experience ovarian failure or early menopause, leading to a loss of bone mineral density (BMD). Loss of BMD may be reduced by use of bisphosphonates, compounds that inhibit the action of osteoclasts (cells that absorb or remove bone tissue). We have conducted a double-blind, randomized, two-center trial to evaluate BMD in women with primary breast cancer who were given the bisphosphonate clodronate (1600 mg/day orally) or placebo for 2 years. METHODS: From August 31, 1990, through March 31, 1996, more than 300 eligible patients had been accrued, randomly assigned to study treatment, given the appropriate primary surgical care and systemic (chemotherapy and/or tamoxifen) therapy, and had completed follow-up for at least 1 year. BMD in the lumbar spine and in the hip, including the trochanteric area, was measured by use of dual-energy x-ray absorptiometry at the beginning of treatment and after 1 and 2 years of treatment. Changes in BMD were calculated as percent changes from the initial readings. Treatment effects for clodronate versus placebo (i.e., mean percent changes in BMD with clodronate minus mean percent changes in BMD with placebo) at 1 and 2 years for individual sites were calculated. RESULTS: After 1 year, the treatment effects for clodronate versus placebo in the lumbar spine, the total hip, and the trochanter, respectively, were as follows: +2.38% (95% confidence interval [CI] = 1.36-3.41), +0.74% (95% CI = -0.13 - 1.60), and +1.29% (95% CI = 0.24-2.34). After 2 years, the corresponding treatment effects were +1.72% (95% CI = 0.12-3.34), +1.85% (95% CI = 0.51-3.20), and +2.30% (95% CI = 0.66-3.94), respectively. CONCLUSIONS: Oral clodronate appears to reduce the loss of BMD in patients who receive treatment for primary breast cancer.

Intermittent interferon and polychemotherapy in metastatic melanoma.

This study was conducted to evaluate the efficacy and the tolerability of a four-drug chemotherapy regimen combined with interferon alpha (IFN) in metastatic melanoma. Between March 1991 and August 1993, 55 patients with advanced melanoma were enrolled for the present multicentre phase II study. Forty-nine patients were eligible and evaluable for toxicity; 48 patients were evaluable for response. The treatment schedule consisted of a 5-day regimen of dacarbazine, vincristine, bleomycin and lomustine, plus 6 x 10(6) IU IFN alpha three times weekly subcutaneously for 2 weeks starting on day 8. The cycle was repeated on day 29. Among the 48 assessable patients, 16 objective responses were seen, yielding a response rate of 33% (95% confidence interval 20%-46%). Seven patients achieved a complete response (CR) of a median of 6+ months (range 1+ to 21+ months) and 9 patients achieved a partial response (PR) of a median of 9 months (range 4-13 months). The median overall survival was 12+ months (range 6+ to 23+ months) for the patients with CR and 15+ months (range 8-20 months) for the patients with PR. Even the survival of the 7 patients with stable disease was fairly long (median 12, range 7-17 months), appearing to be significantly longer than the survival of the 25 patients with progressive disease (median 5, range 1-24+ months). The treatment was moderately well tolerated, although all patients experienced some mild form of toxicity, mostly gastrointestinal symptoms, neurotoxicity and haematotoxicity. Grade 3-4 adverse effects were noted in 39% of the patients. No toxic deaths occurred. It can be concluded that the present regimen produces meaningful responses for patients with metastatic melanoma. A randomised study is needed to determine the effect on survival.