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| |  ICACT: Amsacrine/Cisplatin Combination Offers Low-Toxicity Option for Metastatic Urothelial Cancer By Paula Moyer PARIS, FRANCE -- February 17, 2004 -- Combining amsacrine and cisplatin (Platinol) offers a low-toxicity treatment option to patients with metastatic transitional cell carcinoma of the urothelium and a poor prognosis. The investigative regimen is linked to a significantly lower toxicity than is a currently used combination of methotrexate (Matrax), vinblastine (Velban), doxorubicin (Adriamycin), and cisplatin, also known as M-VAC, said principal investigator Ivan Popov, MD, a medical oncologist with the Institute of Oncology and Radiology in Belgrade, Serbia. He presented the study findings here February 12th at the 15th International Congress of Anti-Cancer Therapy. Dr. Popov said that he and his co-investigators were interested in the amsacrine-cisplatin combination because the subgroup of patients with metastatic bladder cancer and poor prognosis "is seldom a target population for clinical trials," and because combination chemotherapy regimens often are associated with high levels of toxicity and minimal clinical benefit for them. The researchers recruited 30 patients, 22 men and 8 women, who were a median of 64 years old and ranged from 41 to 72 years old. Fifteen each were randomised to the investigative regimen or to M-VAC. All the patients had metastatic disease. In the amsacrine-cisplatin arm, 5 patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 1, 7 had an ECOG performance status of 2, and 3 had a performance status of 3. In the MVAC group, 4 had a performance status of 1; 8 had a performance status of 2; and 3 had a performance status of 3. The majority of the patients had at least 2 metastasis sites. The amsacrine-cisplatin group received 85 mg/m2 of amsacrine on days 1 and 2 and 30 mg/m2 of cisplatin on days 2, 3, 4, and 5. The M-VAC group received 30 mg/m2 of methotrexate on days 1, 15, and 22; 3 mg/m2 of vinblastine on days 2, 15, and 22; 30 mg/m2 of doxorubicin on day 2; and 70 mg/m2 of cisplatin on day 2. The protocol called for the cycles to be repeated every 2 weeks. The patients received a total of 49 cycles in the amsacrine-cisplatin arm, with a median of 3 cycles per patient. In the M-VAC arm, patients received a total of 32 cycles and a median of 2 per patient. Three of the amsacrine-cisplatin patients and 14 of the M-VAC patients required treatment postponements, primarily due to either neutropaenia or thrombocytopaenia. In the investigative arm, patients were able to receive more than 90% of the planned dose intensity of both drugs. However, in the M-VAC arm, patients were able to receive 34% of the planned dose of methotrexate, 34% of the intended dose of vinblastine, 49% of the doxorubicin dose, and 54% of the cisplatin dose. Of the evaluable patients, the investigators documented a similar treatment response in each group; 7 of the 15 amsacrine-cisplatin patients and seven of the 13 M-VAC patients had a response to treatment. The investigators noted the following severe haematological toxicity events, which they defined as grades 3-4: in the amsacrine-cisplatin arm, 40% of patients experienced neutropaenia; 20% developed thrombocytopaenia; 13% developed anaemia; and 2% developed febrile neutropaenia. In the M-VAC group, 73% developed neutropaenia; 27% developed thrombocytopaenia; 13% developed anaemia; and 11% experienced febrile neutropaenia. The 2 groups had similar rates of non-haematological adverse events, typically, alopecia, mucositis, and nausea or vomiting. There were no treatment-related deaths in the amsacrine-cisplatin group; 2 patients in the M-VAC group died of septic shock following neutropaenia. After the first toxicity analysis, investigators decided that the death rate and the rate of serious adverse events in the M-VAC group were unacceptably high. The investigators concluded that the amsacrine-cisplatin regimen may fulfil the need for a low-toxicity chemotherapy regimen for patients with metastatic bladder cancer and poor prognosis. Therefore, they are planning to study amsacrine-cisplatin, as well as other low-toxicity regimens, in this patient population, according to Dr. Popov.
[Study title: "Amsacrine/cisplatin vs. M-VAC in metastatic transitional cell carcinoma of the urothelium: do we have treatment options for poor prognosis patients." Abstract P41]
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