HIV and Anal Cancer

Abdominoperineal resection leading to permanent colostomy was previously thought to be required for all but small anal cancers below the dentate line, with approximately 70% of patients surviving 5 or more years in single institutions,[1] but such surgery is no longer the treatment of choice.[2,3] Radiation therapy alone may lead to a 5-year survival rate in excess of 70%, though high doses (≥60 Gy) may yield necrosis or fibrosis.[4] Chemotherapy concurrent with lower-dose radiation therapy as evidenced in the RTOG-8314 trial, for example, has a 5-year survival rate in excess of 70% with low levels of acute and chronic morbidity, and few patients require surgery for dermal or sphincter toxic effects.[5-10] The optimal dose of radiation with concurrent chemotherapy to optimize local control and minimize sphincter toxic effects is under evaluation as evidenced in the RTOG-9208 trial, for example, but appears to be in the 45 Gy to 60 Gy range.[11,12] Analysis of an intergroup trial that compared radiation therapy plus fluorouracil/mitomycin with radiation therapy plus fluorouracil alone in patients with anal cancer has shown improved results (lower colostomy rates and higher colostomy-free and disease-free survival) with the addition of mitomycin.[13] Radiation with continuous infusion of fluorouracil plus cisplatin is also under evaluation as seen in the RTOG 9811 trial.[14] Standard salvage therapy for those patients with either gross or microscopic residual disease following chemoradiation therapy has been abdominoperineal resection. Alternately, patients may be treated with additional salvage chemoradiation therapy in the form of fluorouracil, cisplatin, and a radiation boost to potentially avoid permanent colostomy.[13]

Because of the small number of cases, information that can only come from patient participation in well-designed clinical trials is needed to improve the management of anal cancer. Patients with stages II, III, and IV disease should be considered candidates for clinical trials. Information about ongoing clinical trials is available from the NCI Web site.

The tolerance of patients with human immunodeficiency virus (HIV) and anal carcinoma to standard fluorouracil/mitomycin chemoradiation is not well defined.[15,16] Patients with pretreatment CD4 counts of less than 200 may have increased acute and late toxic effects;[17,18] chemoradiation doses may require modification in this subset of patients.

References

1. Boman BM, Moertel CG, O'Connell MJ, et al.: Carcinoma of the anal canal. A clinical and pathologic study of 188 cases. Cancer 54 (1): 114-25, 1984.  [PUBMED Abstract]
   
   
2. Stearns MW Jr, Quan SH: Epidermoid carcinoma of the anorectum. Surg Gynecol Obstet 131 (5): 953-7, 1970.  [PUBMED Abstract]
   
   
3. Cummings BJ: The Role of Radiation Therapy With 5-Fluorouracil in Anal Cancer. Semin Radiat Oncol 7 (4): 306-312, 1997.  [PUBMED Abstract]
   
   
4. Cantril ST, Green JP, Schall GL, et al.: Primary radiation therapy in the treatment of anal carcinoma. Int J Radiat Oncol Biol Phys 9 (9): 1271-8, 1983.  [PUBMED Abstract]
   
   
5. Leichman L, Nigro N, Vaitkevicius VK, et al.: Cancer of the anal canal. Model for preoperative adjuvant combined modality therapy. Am J Med 78 (2): 211-5, 1985.  [PUBMED Abstract]
   
   
6. Sischy B: The use of radiation therapy combined with chemotherapy in the management of squamous cell carcinoma of the anus and marginally resectable adenocarcinoma of the rectum. Int J Radiat Oncol Biol Phys 11 (9): 1587-93, 1985.  [PUBMED Abstract]
   
   
7. Sischy B, Doggett RL, Krall JM, et al.: Definitive irradiation and chemotherapy for radiosensitization in management of anal carcinoma: interim report on Radiation Therapy Oncology Group study no. 8314. J Natl Cancer Inst 81 (11): 850-6, 1989.  [PUBMED Abstract]
   
   
8. Cummings BJ: Anal cancer. Int J Radiat Oncol Biol Phys 19 (5): 1309-15, 1990.  [PUBMED Abstract]
   
   
9. Zucali R, Doci R, Bombelli L: Combined chemotherapy--radiotherapy of anal cancer. Int J Radiat Oncol Biol Phys 19 (5): 1221-3, 1990.  [PUBMED Abstract]
   
   
10. Fuchshuber PR, Rodriguez-Bigas M, Weber T, et al.: Anal canal and perianal epidermoid cancers. J Am Coll Surg 185 (5): 494-505, 1997.  [PUBMED Abstract]
    
    
11. Fung CY, Willett CG, Efird JT, et al.: Chemoradiotherapy for anal carcinoma: what is the optimal radiation dose? Radiat Oncol Investig 2(3): 152-6, 1994. 
    
    
12. John M, Pajak T, Flam M, et al.: Dose Escalation in Chemoradiation for Anal Cancer: Preliminary Results of RTOG 92-08 Cancer J Sci Am 2 (4): 205-11, 1996.  [PUBMED Abstract]
    
    
13. Flam M, John M, Pajak TF, et al.: Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. J Clin Oncol 14 (9): 2527-39, 1996.  [PUBMED Abstract]
    
    
14. Rich TA, Ajani JA, Morrison WH, et al.: Chemoradiation therapy for anal cancer: radiation plus continuous infusion of 5-fluorouracil with or without cisplatin. Radiother Oncol 27 (3): 209-15, 1993.  [PUBMED Abstract]
    
    
15. Holland JM, Swift PS: Tolerance of patients with human immunodeficiency virus and anal carcinoma to treatment with combined chemotherapy and radiation therapy. Radiology 193 (1): 251-4, 1994.  [PUBMED Abstract]
    
    
16. Peddada AV, Smith DE, Rao AR, et al.: Chemotherapy and low-dose radiotherapy in the treatment of HIV-infected patients with carcinoma of the anal canal. Int J Radiat Oncol Biol Phys 37 (5): 1101-5, 1997.  [PUBMED Abstract]
    
    
17. Hoffman R, Welton ML, Klencke B, et al.: The significance of pretreatment CD4 count on the outcome and treatment tolerance of HIV-positive patients with anal cancer. Int J Radiat Oncol Biol Phys 44 (1): 127-31, 1999.  [PUBMED Abstract]
    
    
18. Place RJ, Gregorcyk SG, Huber PJ, et al.: Outcome analysis of HIV-positive patients with anal squamous cell carcinoma. Dis Colon Rectum 44 (4): 506-12, 2001.  [PUBMED Abstract]
    
    

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