mesna and Agranulocytosis

Chemotherapy has not significantly altered the overall survival of patients with recurrent squamous cell carcinoma of the head and neck; therefore, the development of new agents is essential. The purpose of the current phase II study was to define the efficacy of ifosfamide in the treatment of recurrent squamous cell carcinoma of the head and neck. All patients were required to have squamous cell carcinoma of the head and neck that had recurred following surgery or radiotherapy or both. Patients may have received prior chemotherapy. Patients were initially treated with ifosfamide 2 g/m2/day for 4 days (dose level 0). Dose level-1 was 2 g/m2/day for 3 days, and dose level-2 was 2 g/m2/day for 2 days. All patients received mesna 400 mg/m2/day prior to and 1,200 mg/m2/day as a continuous infusion after ifosfamide. Thirty-eight patients were enrolled in the study. Five patients were inevaluable for toxicity or response. Overall, the regimen was well tolerated, with grade 4 granulocytopenia the only significant toxicity occurring in 16 patients. Overall, eight of 31 evaluable patients (25.8%) had a major response. Only one of the 10 patients (10%) with prior chemotherapy responded, but seven of the 21 patients (33.3%) with no prior chemotherapy had major responses. Ifosfamide is an active agent in recurrent squamous cell carcinoma of the head and neck. Further studies of ifosfamide in combination with other agents, particularly as induction therapy in patients with locally advanced disease, are warranted.

Topics: Adult; Aged; Agranulocytosis; Antineoplastic Agents, Alkylating; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Ifosfamide; Infusions, Intravenous; Injections, Intravenous; Male; Mesna; Middle Aged; Neoplasm Recurrence, Local; Remission Induction; Survival Rate

Ifosfamide has shown promising single-agent activity in non-small cell lung cancer (NSCLC). We combined ifosfamide (1,800 mg/m2 plus mesna 1,100 mg/m2 by intravenous [IV] continuous infusion daily for 3 days) with cisplatin (20 mg/m2 IV for 3 days) and etoposide (80 mg/m2 IV for 3 days) and treated 41 chemotherapy-naive patients with recurrent or metastatic NSCLC. Fifteen (40.5%) of the 37 evaluable patients had objective responses (1 complete and 14 partial). Patients with good performance status (Zubrod scale 0 or 1) had a higher response rate than the patients with poor performance status (Zubrod scale 2) (11 of 21 patients [52.4%] versus four of 16 [25.0%]), but the difference was not statistically significant (P = .09). Median survival has not been reached, with 17 patients still alive after a median follow-up of 39 weeks (range, 21 to 56). Significant myelosuppression occurred, with granulocytopenia being the dose-limiting toxicity. Overall, treatment was well tolerated. Considering the pooled response rate of 32% with cisplatin/etoposide regimens and the previous experience from our institution, the results with this three-drug regimen are very encouraging, and its further investigation is warranted.

Topics: Adenocarcinoma; Adult; Aged; Agranulocytosis; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cisplatin; Clinical Protocols; Clinical Trials, Phase II as Topic; Etoposide; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Remission Induction; Survival Rate

The purpose of this study was to evaluate the activity of ifosfamide (isophosphamide) in patients with advanced or recurrent leiomyosarcoma not previously exposed to chemotherapy.. This is a phase II groupwide study of the Gynecologic Oncology Group. Thirty-five patients were treated with ifosfamide 1.5 gm/m2 daily intravenously for 5 days with mesna (mercaptoethane sodium sulfonate). Fifty-six patients had received prior abdominal hysterectomy and 15 prior radiotherapy. The dose was reduced to 1.2 gm/m2 daily in patients who had received prior radiotherapy.. Gynecologic Oncology Group grade III or IV granulocytopenia occurred in 4 (11%) patients, and none had grade IV thrombocytopenia. One (2.8%) patient had grade IV neurotoxicity. Partial responses were observed in 6 of 35 (17.2%) patients. The 95% confidence interval for response was 6.6% to 33.7%.. These results indicate that ifosfamide has modest activity in patients with advanced or recurrent leiomyosarcomas of the uterus.

Topics: Adult; Aged; Agranulocytosis; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Ifosfamide; Leiomyosarcoma; Mesna; Middle Aged; Remission Induction; Uterine Neoplasms