Cisplatin-based combined modality therapy for anal carcinoma: a wider therapeutic index

Background: Definitive chemoradiation therapy is the standard of care for anal carcinoma. The chemotherapy regimen comprising 5-fluorouracil (5-FU) and mitomycin-C is the most commonly used among patients with anal carcinoma but causes well documented toxicities. In the current study, the authors evaluated their experience in treating anal carcinoma with combined modality therapy using cisplatin and 5-FU.

Methods: A retrospective analysis was performed of 92 patients with nonmetastatic squamous cell carcinoma of the anus who were treated between 1989 and 1998. The primary tumor and involved lymph nodes received a total dose of 55 grays (Gy) administered in more than 30 daily fractions. Cisplatin (4 mg/m(2)/day) and 5-FU (250 mg/m(2)/day) were given as a continuous infusion, 5 days each week during the entire radiation course. Kaplan-Meier methodology was used to determine local control (LC), disease-free survival (DFS), and overall survival (OS).

Results: Ten patients had T1 or Tx, 43 had T2, 27 had T3, and 12 patients had T4 disease. There were 21 male and 71 female patients. Sixty-five patients (71%) were lymph node negative. With a median follow-up duration of 44 months, the actuarial 5-year OS rate was 85%, the DFS rate was 77%, and the colostomy-free survival rate was 82%. Local recurrences occurred in 16 patients (17%). Distant metastases (DM) occurred in eight patients (9%). Advanced T classification (> T2) predicted lower LC and DFS rates. Advanced N classification (> N1) predicted worse DFS, OS, and DM rates. Greater than 90% of patients completed treatment without significant treatment interruption. Only five patients developed acute toxicities of Radiation Therapy Oncology Group (RTOG) Grade 4 or higher and only three patients developed chronic toxicities of RTOG Grade 4 or higher.

Conclusions: Combined modality therapy with continuous infusion of cisplatin and 5-FU is a well tolerated regimen that results in high rates of LC, OS, and sphincter preservation. These rates are comparable to the best results reported with mitomycin-C and 5-FU. Without the normally severe toxicity, cisplatin-based therapy results in a wider therapeutic index.