Zoledronic acid for the treatment of osteoporosis in patients with beta-thalassemia: results from a single-center, randomized, placebo-controlled trial.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the effect of zoledronic acid (ZA) on thalassemia-induced osteoporosis. DESIGN AND METHODS: We studied 66 thalassemia patients with osteoporosis, who were randomized to receive 4 mg ZA iv, every 6 months (23 patients; group A) or every 3 months (21 patients; group B), or to receive placebo every 3 months (22 patients; group C), for a period of 1 year. Bone mineral density (BMD) of the lumbar spine, femoral neck and wrist was determined before and 12 months after treatment. Pain scores and markers of bone resorption [C-telopeptide of collagen type-I (CTX), 5b-isoform of TRAP], bone formation [bone-alkaline phosphatase (bALP), osteocalcin (OC), C-telopeptide of procollagen type-I (CICP)], and osteoclast stimulators [sRANKL, osteoprotegerin (OPG), osteopontin] were also measured at baseline and before each treatment administration. RESULTS: The values of CTX, bALP, CICP, sRANKL, and OPG were higher in the all patients than in the controls. Patients in group A showed no differences in BMD of all sites at 12 months, while they had reductions in bone pain, bALP, OC and OPG. Conversely patients in group B had a significant increase in their lumbar spine BMD, which was accompanied by dramatic reductions in bone pain, CTX, bALP, CICP, and OC. Patients in group C showed no alteration in BMD of any studied site or in bone pain, while they had an aggravation in bone resorption. INTERPRETATION AND CONCLUSIONS: ZA, at a dose of 4 mg, iv, every 3 months is an effective treatment for increasing BMD and reducing bone resorption in thalassemia-induced osteoporosis.

Treatment of Waldenström's macroglobulinemia with rituximab.

PURPOSE: Waldenström's macroglobulinemia (WM) is a low-grade lymphoplasmacytic lymphoma in which CD20 is usually expressed on tumor cells. There is evidence that patients with WM may benefit from treatment with the anti-CD20 monoclonal antibody rituximab. We performed a prospective phase II study to clearly define the activity of rituximab in patients with this disease. PATIENTS AND METHODS: Twenty-seven patients with WM were treated with rituximab 375 mg/m(2) intravenously (IV) for 4 weeks. Three months after completion of rituximab, patients without evidence of progressive disease received repeat 4-week courses of this agent. All patients were symptomatic, their median age was 72 years, and 15 patients were previously untreated. RESULTS: Twelve patients (44%; 95% confidence interval, 25.5% to 64.7%) achieved a partial response after treatment with rituximab. Median time to response was 3.3 months (range, 2.2 to 7.1 months). Responses occurred in six (40%) of 15 previously untreated patients and in six (50%) of 12 pretreated patients. Patients with a serum immunoglobulin M less than 40 g/L had a significantly higher response rate. The median time to progression for all patients was 16 months, and with a median follow-up of 15.7 months, nine of 12 responding patients remain free of progression. Treatment with rituximab was well tolerated, with approximately one fourth of patients experiencing some mild form of infusion-related toxicity, usually fever and chills. CONCLUSION: Our prospective data indicate that rituximab is well tolerated and active in patients with WM. Previously untreated and pretreated patients seem to benefit equally. Repeat 4-week courses of rituximab may prolong the duration of response of the disease, but this observation requires confirmation in prospective, randomized trials. Furthermore, studies that will combine rituximab with chemotherapy may be relevant.

Docetaxel and gemcitabine combination, as first-line treatment, in patients with extensive disease small-cell lung cancer. A phase II study of the Hellenic Cooperative Oncology Group.

There is some evidence that taxanes and gemcitabine are effective antitumor agents against small-cell lung cancer (SCLC). A total of 20 chemotherapy-naive patients with extensive disease (ED) SCLC, were treated as a part of the first step of a phase II study, with docetaxel 50 mg/m(2) and gemcitabine 1000 mg/m(2), both administered on day 1 and 8 every 3 weeks up to a total of six cycles. For patients who progressed after the first cycle or had stable disease after the second cycle of chemotherapy, protocol treatment was stopped and further treatment with the standard cisplatin or carboplatin-etoposide combination was administered. Patients were in the vast majority male smokers with a good performance status. A total of 72 cycles was delivered while patients managed to receive the 78 and 84% of the planned dose of docetaxel and gemcitabine, respectively. Only six patients responded partially and the trial ended prematurely since at least seven responses were required among the first 19 patients. With a median follow-up of 13 months, median time to progression (TTP) was 8 months and median survival 9.6 months. Hematological and non-hematological toxicity was generally acceptable while patients tolerated their treatment reasonably well. In conclusion, docetaxel-gemcitabine showed a modest response rate in chemotherapy-naive patients with ED SCLC.

Primary treatment of low-grade non-Hodgkin's lymphoma with the combination of fludarabine and mitoxantrone: a phase II study of the Hellenic Cooperative Oncology Group.

The treatment of patients with recurrent low-grade lymphoma with the combination of fludarabine, mitoxantrone and dexamethasone has been associated with significant activity but has also caused frequent infectious complications. We designed a phase II study for previously untreated patients with the combination of fludarabine and mitoxantrone but without steroids. Our aim was to assess the activity of this combination as primary treatment for low-grade lymphoma and to avoid the additional immunosuppression induced by dexamethasone. Twenty seven patients with low-grade lymphoma received fludarabine 25 mg/m2/day i.v. on days 1-3 and mitoxantrone 10 mg/m2 i.v. on day 1. The treatment was repeated every 28 days for a maximum of six cycles. Twenty patients (74%) achieved an objective response including 12 (44%) complete and 8 (30%) partial responses. The main toxicity was grade III or IV neutropenia, which occurred in 40% of patients but there were no severe opportunistic infections. The median time to progression for all patients was 32 months. With a median follow-up of 33.4 months, six patients have died and the probability of survival at 3 years is 75%. We conclude that the fludarabine and mitoxantrone regimen is safe and effective for newly diagnosed patients with low-grade lymphoma who require treatment. Prospective randomized trials are needed in order to assess the impact of this treatment on patients' survival.

The combination of estramustine, vinorelbine, and mitoxantrone in hormone-refractory prostate cancer: a Phase II feasibility study conducted by the Hellenic Cooperative Oncology Group.

OBJECTIVES: To evaluate the safety profile and therapeutic value of the combination of estramustine, mitoxantrone, and vinorelbine in the treatment of hormone-refractory prostate cancer. METHODS: Fifty-two patients with hormone-refractory prostate cancer were included in the study. Median age was 70 years (range, 49 to 100 years), World Health Organization performance status ranged from 0 to 2. The treatment schedule consisted of estramustine capsules (140 mg 3 times daily on days 1 to 3 and days 8 to 10 per os), intravenous mitoxantrone (12 mg/m2 on day 2), and intravenous vinorelbine (25 mg/m2 on day 2 and day 9), given in a 3-week cycle. RESULTS: Thirty-one percent of patients with measurable soft-tissue disease demonstrated an objective response, which included six complete and ten partial responses in all involved organs (bone responses not included). Twenty-nine patients (56%) had a greater than 50% reduction in serum prostate-specific antigen level. The median duration of response was 6.9 months, and the median survival for all patients was 14.5 months. CONCLUSIONS: The combination of estramustine, vinorelbine, and mitoxantrone is safe, well tolerated, and relatively active in patients with hormone-refractory prostate cancer.

Combination of LHRH analog with somatostatin analog and dexamethasone versus chemotherapy in hormone-refractory prostate cancer: a randomized phase II study.

OBJECTIVES: To evaluate prospectively the combination of a luteinizing hormone-releasing hormone analog with a somatostatin analog and dexamethasone in patients with hormone-refractory prostate cancer (HRPC) in a randomized Phase II study. HRPC presents a challenging therapeutic problem. Salvage chemotherapy is the usual approach at this stage of the disease. The combination of a luteinizing hormone-releasing hormone analog with a somatostatin analog and dexamethasone has produced objective clinical responses in HRPC. METHODS: Forty patients with HRPC were randomized to receive one of two treatments. Group 1 underwent chemotherapy (estramustine 140 mg three times daily and etoposide 100 mg orally for 21 days) and group 2 the combination of a somatostatin analog (lanreotide 30 mg intramuscularly every 14 days) and dexamethasone (4 mg tapered to 1 mg), in addition to androgen ablation by orchiectomy or a luteinizing hormone-releasing hormone analog (triptorelin 3.75 mg intramuscularly every 28 days). The clinical and prostate-specific antigen (PSA) response, overall survival, time to progression, and toxicity were compared between the two groups. RESULTS: The data of 20 patients in group 1 and 18 in group 2 were analyzed. The demographic and clinical data were similar in the two groups at study entry. A PSA response (decrease of greater than 50%) was observed in 45% of group 1 and 44% of group 2. The difference was not statistically significant. A partial clinical response was observed in 29% and 30% of groups 1 and 2, respectively. Again, the difference was not statistically significant. Changes in performance status and pain score during treatment were not significantly different in the two groups. Hematologic toxicity was more frequent in group 1 (80% of patients), and mild diabetes was more frequent in group 2 (22% of patients). The overall survival was 18.8 months in group 1 and 18 months in group 2 (not statistically significant). The time to progression was 6 versus 4 months and, in the PSA responder subgroup, it was 8 versus 7.7 months in groups 1 and 2, respectively (neither difference was statistically significant). CONCLUSIONS: The results of our randomized Phase II study indicated that the new combination treatment (luteinizing hormone-releasing hormone analog, somatostatin analog, and dexamethasone) may be equally effective as salvage chemotherapy in patients with HRPC in terms of the clinical and PSA response, overall survival, and time to progression. A larger prospective Phase III trial is required to confirm our observations.