No abstract

BACKGROUNDMalignant pleural mesothelioma (MPM) is increasing rapidly worldwide. Currently, pemetrexed plus cisplatin chemotherapy showed a survival advantage versus cisplatin alone. No impact on patient survival of surgery, radiotherapy, or their combination has been demonstrated.METHODSEight centers in northeastern Italy participated in a Phase II multicenter study. Chemotherapy was comprised of carboplatin area under the concentration‐time curve 5 on Day 1 and gemcitabine 1000 mg/m2 on Days 1, 8, and 15. This cycle was repeated every 4 weeks.RESULTSBetween July 1996 and September 2000, 50 patients were treated. Of the sample, 68% were males, 88% had a Eastern Cooperative Oncology Group performance status score of 0–1, 56% had Stage I–II disease, 68% had epithelioid histology, and 62% had no previous treatments. The delivered dose intensity of gemcitabine was 617 mg/m2 per week, which was 82% of the planned dose (750 mg/m2 per week). For carboplatin, the delivered dose intensity was 80 mg/m2 per week. Overall, 44% of 15th day doses were omitted or reduced. Twenty‐six percent of the patients had partial responses (95% confidence interval: 15–40%) and 24% had disease progression. None of the patients had complete responses. The median response duration was 55 weeks (range, 13–113 weeks). Patients had good clinical benefit. For example, 46% had improved dyspnea, 40% improved in weight, and 26% experienced pain reduction. Patients developed Grade 3–4 leukopenia during 18 cycles (11%) of chemotherapy. Grade 3–4 thrombocytopenia occurred more frequently, i.e., there were 24 episodes (15%) among 17 patients. Grade 3 anemia developed among patients during eight cycles (5%). None of the patients developed Grade 3–4 nonhematologic toxicity. The median survival of this sample of patients was 66 weeks with 53%, 30%, and 20% of patients alive at 1, 2, and 3 years, respectively. The median progression‐free survival period was 40 weeks.CONCLUSIONSThe gemcitabine/carboplatin combination is a valid option in the treatment of MPM due to its acceptable toxicity profile, the good response rate, and the clinical benefit to patients. Minor adjustments in schedule (3‐week cycles instead of 4‐week cycles) would permit a more optimal treatment administration. Cancer 2003;97:2791–7. © 2003 American Cancer Society.DOI 10.1002/cncr.11405

High-grade malignant gliomas are inevitably fatal, despite every effort to improve this prognosis, including various radiotherapeutic modalities, radio- and chemotherapeutic associations, and combinations of several drugs. High-dose chemotherapy and autologous bone-marrow transplantation (ABMT) have been increasingly used in the last 10 years for solid tumors, and several phase II studies in high-grade glioma patients have been conducted in the setting of both adjuvant treatment and recurrent disease. The most frequently used drug in the conditioning regimens in BCNU at doses higher than that employed by other regimens in other pathologies (800-1000 mg/m2). These dosages involve a high toxicity that is not balanced by a significant improvement in survival. New drugs and/or regimens must be tested in randomized trials.

Abstract. Pegylated liposomal doxorubicin (PLD) has the advantage of delivering active anthracycline directly to the tumor site, while exposing the patient to a lesser degree of doxorubicin-associated toxicities. Recently, a regimen in which paclitaxel is infused weekly over 1 h produced substantial antitumor activity with little myelosuppression. We designed a phase II trial to study the efficacy and toxicity of 10 mg/m 2 PLD on Days 1, 8 and 15, plus 70 mg/m 2 paclitaxel weekly in patients with untreated metastatic breast cancer and a high risk of cardiotoxicity. The study included 35 patients, with 31 (88.5%) evaluable for efficacy and 35 (100%) for toxicity. A total of 28 patients (80%) had two or more sites of disease. Overall, 4 complete and 16 partial responses were noted with an overall response rate of 64.5%, with 6 cases of stable and 5 cases of progressive disease. Toxicity was found to be manageable in that the only grade 3-4 side effects recorded were palmar-plantar erythrodysesthesia, 8.5%; mucositis, 2.8%; leucopenia, 12.5%; anemia, 2.8% and AST/ALT, 2.8%. No cardiotoxicity was observed. In conclusion, weekly PLD plus paclitaxel appears to be a well-tolerated and effective approach for metastatic breast cancer patients with a high risk of cardiotoxicity.

No abstract