Phase II Study of Ifosfamide Combined with Mesna Uroprotection in Advanced Non-Small-Cell Lung Carcinoma and Other Solid Tumors

Abstract

Thirty six patients with advanced solid tumors (24 lung: 3 oat-cell, 14 squamous, 7 adenocarcinomas, 3 soft tissue sarcomas, 6 breast carcinomas; 1 seminoma; 2 ovarian adenocarcinomas) entered a phase II study of high-dose ifosfamide (IF) administered in combination with the uroprotective agent sodium 2-mercapto-ethane-sulfonate (Mesna). Fourteen patients had prior treatment; most patients with lung cancer (22/24) were previously untreated; all had measurable disease. The patients median age was 59 (range 31–74). IF was given at 1.8 g/m2 days 1–5 q 4 weeks. Mesna was given after each IF injection at 0, 4 and 8 h randomly, either i.v. (0.36 g/m2) or orally (0.72 g/m2). Twenty-four patients had ≥ 3 courses of therapy, 9 had 2 courses, and 3 had only 1 course; 129 courses were evaluated for toxicity. Mesna was given orally (17 patients, 57 courses) or i.v. (19 patients, 72 courses). The following side-effect were observed: no gross hematuria, microhematuria (14 courses), transitory mild proteinuria (34 courses), leukopenia grade I-II ECOG (26 courses), anemia grade I ECOG (31 courses), 1 case of pancytopenia, alopecia (31 patients), nausea (moderate, 33 courses; severe, 6 courses), vomiting (moderate, 17 courses; severe, 1 course). Five patients showed a partial response (1 oat-cell carcinoma, 2 with squamous lung cancer, 1 with ovarian carcinoma, 1 with breast carcinoma), 14 showed a minor response (2 patients with oat-cell carcinoma, 2 with lung adenocarcinoma, 5 with squamous lung cancer, 1 with seminoma, 1 with sarcoma, 1 with ovarian carcinoma), and 14 showed progression of disease (7 patients with squamous cell lung cancer, 4 with lung adenocarcinoma, 1 with sarcoma, 2 with breast carcinoma). Considering partial plus minor responses, ifosfamide produced some degree of tumor reduction (PR+MR) in 12/23 (52.1 %) lung cancer patients. The data reported support the conclusions that Mesna can prevent high-dose IF bladder toxicity, that IF is active in advanced solid tumors, including lung cancer, and that the IF + Mesna combination is a generally safe treatment procedure.