Cisplatin-based combined modality therapy for anal carcinoma: a wider therapeutic index.
ABSTRACT 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.
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).
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.
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.
Article: Chemoradiotherapy with or without consolidation chemotherapy using cisplatin and 5-fluorouracil in anal squamous cell carcinoma: long-term results in 31 patients.[show abstract] [hide abstract]
ABSTRACT: The objectives of this study were to evaluate long-term results of concurrent chemoradiotherapy (CRT) with 5-fluorouracil and cisplatin and the potential benefit of consolidation chemotherapy in patients with anal squamous cell carcinoma (ASCC). Between January 1995 and February 2006, 31 patients with ASCC were treated with CRT. Radiotherapy was administered at 45 Gy over 5 weeks, followed by a boost of 9 Gy to complete or partial responders. Chemotherapy consisted of 5-fluorouracil (750 or 1,000 mg/m2) daily on days 1 to 5 and days 29 to 33; and, cisplatin (75 or 100 mg/m2) on day 2 and day 30. Twelve patients had T3-4 disease, whereas 18 patients presented with lymphadenopathy. Twenty-one (67.7%) received consolidation chemotherapy with the same doses of 5-fluorouracil and cisplatin, repeated every 4 weeks for maximum 4 cycles. Nineteen patients (90.5%) completed all four courses of consolidation chemotherapy. After CRT, 28 patients showed complete responses, while 3 showed partial responses. After a median follow-up period of 72 months, the 5-year overall, disease-free, and colostomy-free survival rates were 84.7%, 82.9% and 96.6%, demonstrating that CRT with 5-fluorouracil and cisplatin yields a good outcome in terms of survival and sphincter preservation. No differences in 5-year OS and DFS rates between patients treated with CRT alone and CRT with consolidation chemotherapy was observed. our study shows that CRT with 5-FU and cisplatin, with or without consolidation chemotherapy, was well tolerated and proved highly encouraging in terms of long-term survival and the preservation of anal function in ASCC. Further trials with a larger patient population are warranted in order to evaluate the potential role of consolidation chemotherapy.BMC Cancer 02/2008; 8:8. · 3.01 Impact Factor
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ABSTRACT: The clinical features, treatment modality approaches in clinical practice, and prognostic factors for anal canal carcinoma patients were retrospectively analyzed. Between October 1994 and December 2005, 50 patients with anal canal cancer were treated at Samsung Medical Center, Seoul, Korea. After a median follow up of 37.8 months (range, 6.6-136.1 months), the 5-year and 10-year survival rates for the 38 patients with early and locally advanced squamous and cloacogenic carcinoma (squamous cell carcinoma and cloacogenic carcinoma) were 74.8% and 66.5%, respectively. The 5-year survival and disease-free survival rates (DFS) of the 31 patients who received chemoradiation therapy (CRT) were 83.6% and 74.3%, respectively. The overall and DFS could not be determined for the adenocarcinoma group due to the small number of cases (n=8). Univariate analysis showed that tumor size (p=0.04) and inguinal node status (p=0.04) significantly influenced patient survival in patients with squamous cell and cloacogenic carcinomas. Furthermore, univariate analysis also showed that, inguinal node status influenced patient survival in the adenocarcinoma group. Multivariate analysis showed that inguinal node metastasis is a single independent prognostic variable for survival (p=0.04) in patients with squamous cell and cloacogenic carcinomas. Combined CRT has been adopted as standard treatment with outcomes that are comparable to those reported in randomized clinical trials. Due to the rarity and complexity of anal canal carcinoma, interdepartmental cooperation is required for disease treatment. Thus, proper treatment of patients should incorporate a team-approach and should be available to as many patients as possible.Yonsei Medical Journal 11/2007; 48(5):827-32. · 1.14 Impact Factor