Combined preoperative radiation and chemotherapy for squamous cell carcinoma of the anal canal.

Nigro ND, Seydel HG, Considine B, Vaitkevicius VK, Leichman L, Kinzie JJ

Twenty-eight patients with squamous cell carcinoma of the anal canal were treated by preoperative radiation therapy and chemotherapy. The radiation therapy was given for 3000 rad (30 Gy) at 200 rad per day, 5 days a week, to the primary tumor with margin and to the pelvic and inguinal lymph nodes. Chemotherapy was given in the form of 5-fluorouracil infusion 1000 mg/m2 on days 1-4 of the radiation therapy and repeated on days 29-32 of the treatment regimen. Mitomycin C was given in the form of intravenous bolus for 15 mg/m2 on day 1. Surgery was done 4-6 weeks following the last day of radiation treatment. Twelve patients underwent anteroposterior resection, and seven of the 12 had no residual tumor in the surgical specimen, while one patient had microscopic tumor only. An additional 14 patients had complete clinical disappearance of their tumor, and, on excision of the scar, it was found free of microscopic cancer. Two other patients are clinically free of tumor but had no biopsy after therapy. While transient proctitis leukopenia and thrombocytopenia were moderate to severe, no serious complications were observed in these patients. Twenty-two patients are free of tumor and alive one to eight years after treatment. One patient died a cardiac death without tumor four years after surgery. Four patients, all with residual tumor in the specimen, have died of cancer. Their primary lesions were more than 7 cm in maximum diameter at initial examination. One patient died of disseminated disease with no local recurrence after abdominal perineal resection.

Rays 1997 Jul-Sep;22(3):393-9

Conservative treatment of anal carcinoma with chemotherapy and radiation therapy.

Myerson RJ

Mallinckrodt Institute of Radiology, Washington University Medical Center, Saint Louis, Missouri 63110, USA.

Carcinoma of the anus is a disease that is well treated with chemoradiation therapy. Moderate doses of radiation therapy provide excellent results for T1 lesions and, when salvage treatment is included, for T2 and T3 lesions. Two recently completed European trials (EORTC and UKCCCR) have compared treatment with radiation therapy alone with chemoradiation. Both trials showed a better disease-free survival and a better colostomy-free survival when chemotherapy was added. In the United States, the RTOG has completed a trial evaluating the role of mitomycin-C. RTOG 87-04 compared results with RT plus 5FU plus mitomycin-C: this addition improved disease-free survival and colostomy-free survival. The post-treatment follow-up of patients with anal carcinoma is critical since approximately half of patients with persistent or recurrent disease can be salvaged, frequent follow-up visits with careful physical exam are mandatory.

Semin Radiat Oncol 1997 Oct;7(4):306-312

The Role of Radiation Therapy With 5-Fluorouracil in Anal Cancer.

Cummings BJ

Department of Radiation Oncology, Princess Margaret Hospital, Toronto, ON, Canada

The most commonly used initial treatment of primary epidermoid cancer of the anal canal is radiation combined with concurrent 5-fluorouracil (5-FU) and mitomycin. Randomized trials have shown that these drugs, when combined with split-course or moderate-dose radiation, are superior to the same doses of radiation delivered without drugs. In another trial, the addition of mitomycin to 5-FU resulted in a better outcome thand when 5-FU alone was combined with radiation. Studies are in progress to evaluate treatment with radiation plus 5-FU and cisplatin; this combination has also produced high rates of tumor response in preliminary studies. The optimal schedules and doses of 5-FU to combine with radiation are not known-common usage favors 96- or 120-hour infustions of 5-FU at a dose of 750 to 1,000 mg/m(2)/24 hours, generally administered as one or two courses concurrently with conventional once-daily fractionated radiation. It is unclear whether 5-FU in these combinations is acting as a cytotoxic agent, a radiosensitizer, or both. Despite these uncertainties, empiric clinical studies have led to the development of effective treatment regimens that allow conservation of anorectal function in the majority of patients with anal cancer.

J Clin Oncol 1997 May;15(5):2040-9

Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the European Organization for Research and Treatment of Cancer Radiotherapy and Gastrointestinal Cooperative Groups.

Bartelink H, Roelofsen F, Eschwege F, Rougier P, Bosset JF, Gonzalez DG, Peiffert D, van Glabbeke M, Pierart M

Department of Radiotherapy, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Huis, Amsterdam, The Netherlands. hbart@nki.nl

From 1987 to 1994, 110 patients were randomized between radiotherapy alone and a combination of radiotherapy and chemotherapy. The patients had T3-4NO-3 or T1-2N1-3 anal cancer. Radiotherapy consisted of 45 Gy given in 5 weeks, with a daily dose of 1.8 Gy. After a rest period of 6 weeks, a boost of 20 or 15 Gy was given in case of partial or complete response, respectively. Surgical resection as part of the primary treatment was performed if possible in patients who had not responded 6 weeks after 45 Gy or with residual palpable disease after the completion of treatment. Chemotherapy was given during radiotherapy: 750 mg/m2 daily fluorouracil as a continuous infusion on days 1 to 5 and 29 to 33, and a single dose of mitomycin 15 mg/m2 administered on day 1. RESULTS: The addition of chemotherapy to radiotherapy resulted in a significant increase in the complete remission rate from 54% for radiotherapy alone to 80% for radiotherapy and chemotherapy, and from 85% to 96%, respectively, if results are considered after surgical resections. This led to a significant improvement of locoregional control and colostomy-free interval (P = .02 and P = .002, respectively), both in favor of the combined modality treatment. The locoregional control rate improved by 18% at 5 years, while the colostomy-free rate at that time increased by 32% by the addition of chemotherapy to radiotherapy. The survival rate remained similar in both treatment arms. Event-free survival, defined as free of locoregional progression, no colostomy, and no severe side effects or death, showed significant improvement (P = .03) in favor of the combined-treatment modality. The 5-year survival rate was 56% for the whole patient group. CONCLUSION: The concomitant use of radiotherapy and chemotherapy resulted in a significantly improved locoregional control rate and a reduction of the need for colostomy in patients with locally advanced anal cancer without a significant increase in late side effects.

Lancet 1996 Oct 19;348(9034):1049-54

Epidermoid anal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. UKCCCR Anal Cancer Trial Working Party. UK Co-ordinating Committee on Cancer Research.

From 856 patients considered for entry to our multicentre trial, 585 patients were randomised to receive initially either 45 Gy radiotherapy in twenty or twenty-five fractions over 4-5 weeks (290 patients) or the same regimen of radiotherapy combined with 5-fluorouracil (1000 mg/m2 for 4 days or 750 mg/m2 for 5 days) by continuous infusion during the first and the final weeks of radiotherapy and mitomycin (12 mg/m2) on day 1 of the first course (295 patients). We assessed clinical response 6 weeks after initial treatment: good responders were recommended for boost radiotherapy and poor responders for salvage surgery. The main endpoint was local-failure rate (> or = 6 weeks after initial treatment); secondary endpoints were overall and cause-specific survival. Analysis was by intention-to-treat. FINDINGS: In the radiotherapy and CMT arms, respectively, five and three were ineligible, and six and nine died 6 weeks after initial treatment. After a median follow-up of 42 months (interquartile range 28-62), 164 of 279 (59%) radiotherapy patients had a local failure compared with 101 of 283 (36%) CMT patients. This gave a 46% reduction in the risk of local failure in the patients receiving CMT (relative risk 0.54, 95% CI 0.42-0.69, p < 0.0001). The risk of death from anal cancer was also reduced in the CMT arm (0.71, 0.53-0.95, p = 0.02). There was no overall survival advantage (0.86, 0.67-1.11, p = 0.25). Early morbidity was significantly more frequent in the CMT arm (p = 0.03), but late morbidity occurred at similar rates. INTERPRETATION: Our trial shows that the standard treatment for most patients with epidermoid anal cancer should be a combination of radiotherapy and infused 5-fluorouracil and mitomycin, with surgery reserved for those who fall on this regimen.

Cancer 1999 Jan 1;85(1):26-31

Treatment of anal carcinoma in the elderly: feasibility and outcome of radical radiotherapy with or without concomitant chemotherapy.

Allal AS, Obradovic M, Laurencet F, Roth AD, Spada A, Marti MC, Kurtz JM

Division of Radiation Oncology, University Hospital, Geneva, Switzerland.

From January 1976 through June 1996, invasive anal squamous cell carcinoma was diagnosed in 58 patients age > or = 75 years. Curative treatment was administered to 47 patients (81%), of whom 42 received radiotherapy (RT), either used alone (21) or associated with concomitant chemotherapy (CT). RT was administered in two sequences, the first in which a median dose of 39.6 gray (Gy) was delivered with megavoltage photon beams, followed (after a median interval of 43 days) by a boost with either brachytherapy or external beam (median dose, 20 Gy). CT started on Day 1 and generally consisted of 1 cycle of mitomycin C (MMC; median dose, 9.5 mg/m2) and a 96-hour infusion of 5-fluorouracil (5-FU; median dose, 600 mg/m2/day). The median follow-up for all patients was 48 months (range, 5-163 months). RESULTS: Of 40 patients (95%) who completed curative treatment, acute toxicity resulted in shortening of the planned first irradiation sequence in 2 patients (1 in each group) and an unplanned treatment break in 11 patients (4 in the RT group and 7 in the RT-CT group). Grade 2 and 3 acute reactions (RTOG) were observed in 43% and 54% of patients, respectively. Among all Grade 3 reactions, 32% occurred in the RT group and 68% in the RT-CT group. In patients receiving RT-CT, Grade 2-3 leukopenia was observed in 25% of patients, Grade 2-3 fatigue was observed in 58% of patients, and Grade 2 cardiac toxicity related to 5-FU occurred in 1 patient. At 5 years, the overall survival was 54% (49% and 59% for the RT and RT-CT groups, respectively, P = 0.28), and the actuarial local control rate was 78.5% (73% and 83% for the RT and RT-CT groups, respectively, P=0.36). Five patients presented with Grade 3-4 late complications, all of them in the RT-CT group. CONCLUSIONS: The current series confirms the feasibility of sphincter-conserving treatment for elderly patients who present with anal carcinoma. Rates of acute or late complications appeared similar to those observed in younger patients, and the oncologic results were at least as favorable as those commonly reported.

J Clin Oncol 1996 Sep;14(9):2527-39

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.

Flam M, John M, Pajak TF, Petrelli N, Myerson R, Doggett S, Quivey J, Rotman M, Kerman H, Coia L, Murray K

University of California, San Francisco, Fresno, USA. MSLEVEN@SAMC.com

PURPOSE: Definitive chemoradiation (CR) has replaced radical surgery as the preferred treatment of epidermoid carcinoma of the anal canal. To determine the importance of mitomycin (MMC) in the standard CR regimen and to assess the role of salvage CR in patients who have residual tumor following CR, a phase III randomized trial was undertaken by the Radiation Therapy Oncology Group (RTOG)/Eastern Cooperative Oncology Group (ECOG). PATIENTS AND METHODS: Between August 1988 and December 1991, 310 patients were randomized to receive either radiotherapy (RT) and fluorouracil (5-FU) or radiotherapy, 5-FU, and MMC. Of 291 assessable patients, 145 received 45 to 50.4 Gy of pelvic RT plus 5-FU at 1,000 mg/m2/d for 4 days, and 146 received RT, 5-FU, and MMC (10 mg/m2 per dose for two doses). Patients with residual tumor on posttreatment biopsy were treated with a salvage regimen that consisted of additional pelvic RT (9 Gy), 5-FU, and cisplatin (100 mg/m2). RESULTS: Posttreatment biopsies were positive in 15% of patients in the 5-FU arm versus 7.7% in the MMC arm (P = .135). At 4 years, colostomy rates were lower (9% v 22%; P = .002), colostomy-free survival higher (71% v 59%; P = .014), and disease-free survival higher (73% v 51%; P = .0003) in the MMC arm. A significant difference in overall survival has not been observed at 4 years. Toxicity was greater in the MMC arm (23% v 7% grade 4 and 5 toxicity; P < or = .001). Of 24 assessable patients who underwent salvage CR, 12 (50%) were rendered disease-free. CONCLUSION: Despite greater toxicity, the use of MMC in a definitive CR regimen for anal cancer is justified, particularly in patients with large primary tumors. Salvage CR should be attempted in patients with residual disease following definitive CR before resorting to radical surgery.

Cancer J Sci Am 1996 Jul;2(4):205

Dose Escalation in Chemoradiation for Anal Cancer: Preliminary Results of RTOG 92-08.

John M, Pajak T, Flam M, Hoffman J, Markoe A, Wolkov H, Paris K

Central California Cancer Research Group, University of California, San Francisco, and St. Agnes Hospital, Fresno, California

PURPOSE: Radiation Therapy Oncology Group experience with chemoradiation for anal cancer has shown a local failure rate of 20% to 30% with radiotherapy doses of 45 to 50 cGy. This study was undertaken to assess the effect of higher radiotherapy doses on toxicity, local control, and survival in this disease. MATERIALS AND METHODS: Forty-seven patients with anal cancers measuring >/= 2 cm were treated with a concurrent combination of two cycles of 5-fluorouracil infusion (1000 mg/m2 over 24 hrs for 4 days) and mitomycin C (10 mg/m2 bolus) plus 59.6 Gy of pelvic and perineal radiotherapy administered over 8.5 weeks, including a 2-week rest period. Patients were followed for toxicity, disease status, and colostomy-free survival. Twenty-three (49%) patients had advanced (T3-4) primary tumors; 42 (92%) patients had N0 disease, and 36 (77%) patients had squamous histology. For perspective, a comparative analysis was made with 147 patients treated on the previous RTOG protocol for anal cancers (RTOG 87-04) with identical chemotherapy but radiotherapy doses of 40 to 50.4 Gy. RESULTS: Transient hematologic and skin toxicity predominated during treatment or in early follow-up. One patient developed septicemia and died of multiple gastrointestinal toxicities. Twelve (26%) patients had greater than grade 3 complications and, of these, 9 (20%) had hematologic side effects alone. A comparative analysis with 147 patients treated on RTOG protocol 87-04 showed no significant differences in pretreatment characteristics of disease extent, performance status, or histology. A mandatory 2-week split in the current chemoradiation protocol contrasted with 12% of patients having a 2-week or greater treatment break in RTOG 87-04. Patients treated on the current protocol (RTOG 92-08) had a markedly lower incidence of >/= grade 3 dermal toxicity (34% vs. 55%) but a higher colostomy rate at 1 year (23% vs. 6%) and at 2 years (30% vs. 7%) compared with RTOG 87-04. CONCLUSIONS: Numerical increases in radiotherapy dose over those used in conventional chemotherapy regimens for anal cancers do not appear to increase local control when given in split-course fashion. For higher radiotherapy doses (> 50 Gy) to increase local control, radiation may have to be given in continuous fashion, which almost certainly means that our threshold of acceptable acute toxicity, particularly dermal toxicity, may have to be raised.

Radiother Oncol 1999 Sep;52(3):239-43

Curative-intent radiation therapy in anal carcinoma: quality of life and sphincter function.

Vordermark D, Sailer M, Flentje M, Thiede A, Kolbl O

Department of Radiation Oncology, University of Wurzburg, Germany.

In 22 colostomy-free survivors of curative-intent radiation therapy or chemoradiation for anal carcinoma, measurement of the Gastrointestinal Quality of Life Index (GIQLI) revealed a mean 114 of a maximum 144 points, as compared to 121 in healthy volunteers (n = 150) and 113 in patients with benign anorectal diseases (n = 325). Sixteen patients underwent anorectal manometry to determine anal sphincter length (SL), resting pressure (RP), maximum squeeze pressure (MSP), rectal compliance (RC) and relaxation of the internal anal sphincter (RIAS). SL, RP and MSP were significantly lower in anal carcinoma patients than in healthy volunteers. Complete continence was detected in 56% of patients.

Int J Radiat Oncol Biol Phys 1998 Jul 1;41(4):863-7

Induction chemotherapy and radiotherapy in loco-regionally advanced epidermoid carcinoma of the anal canal.

Svensson C, Goldman S, Friberg B, Glimelius B

The Oncological Department of Southern Stockholm, Huddinge University Hospital, Sweden.

PURPOSE: To evaluate the efficacy of induction chemotherapy in combination with radiotherapy for treatment of loco-regionally advanced epidermoid anal carcinoma. METHODS AND MATERIALS: Thirty-one patients diagnosed during the period 1989-1994 with loco-regionally advanced cancer of the anal canal (phiTmax > or = 4 cm or T4 or N+) were treated with induction chemotherapy consisting of one to three courses of carboplatin (300-375 mg/m2 i.v.) and 5-fluorouracil [5,000 mg/(m2 x 120 h) i.v.] followed by external beam irradiation +/- surgery. RESULTS: The toxicity of the chemotherapy was low. Twenty-nine patients were tumor free after the primary therapy. Kaplan-Meier analyses were made for overall survival, tumor-specific survival, freedom from recurrence, preservation of sphincter, and event-free survival. For these end points the 5-year data were 67, 85, 80, 69, and 51%, respectively. CONCLUSION: The results are promising but a well-designed randomized trial is needed to further elucidate the role of induction chemotherapy in the treatment of loco-regionally advanced anal carcinoma.

Int J Radiat Oncol Biol Phys 1991 Oct;21(5):1115-25

Epidermoid anal cancer: treatment by radiation alone or by radiation and 5-fluorouracil with and without mitomycin C.

Cummings BJ, Keane TJ, O'Sullivan B, Wong CS, Catton CN

Department of Radiation Oncology, Princess Margaret Hospital Toronto, Ontario, Canada.

One hundred ninety-two patients with primary epidermoid cancer of the anal canal were treated by a series of prospectively designed, sequential non-randomized protocols of radiation alone (RT), radiation with concurrent 5-Fluorouracil and Mitomycin C (FUMIR), or radiation with concurrent 5-Fluorouracil only (FUR). The 5-year cause-specific survival rates were 69% overall, 68% RT, 76% FUMIR, 64% FUR. The primary tumor was controlled by radiation with or without chemotherapy in 68% (130/191) overall, 56% (32/57) by RT, 86% (59/69) by FUMIR, 60% (39/65) by FUR. The results with FUMIR were significantly better than with either RT alone or FUR, and except in tumors up to 2 cm in size, this superiority was found in all T stages. Regional lymph node metastases were controlled in 33 of 38 (87%) overall. The finding of clinically detectable regional lymph node metastases at presentation did not affect survival significantly in any treatment group. Anorectal function was preserved in 88% of the patients in whom the primary tumor was controlled, and in 64% overall. The delivery of 5FU and MMC concurrently with uninterrupted radical irradiation, 50 Gy in 20 fractions in 4 weeks, produced severe acute and late normal tissue morbidity. Split course treatment, and reduction of the daily fractional dose to 2 Gy, diminished the severity of normal tissue damage. Omission of Mitomycin C reduced acute hematological toxicity, but was associated with a decreased primary tumor control rate. The most effective treatment protocols as measured by survival rates, primary anal tumor control rates, and the likelihood of conservation of anorectal function included the administration of both Mitomycin C and 5-Fluorouracil concurrently with radiation therapy.

Int J Radiat Oncol Biol Phys 1997 Oct 1;39(3):651-7

Time-dose considerations in the treatment of anal cancer.

Constantinou EC, Daly W, Fung CY, Willett CG, Kaufman DS, DeLaney TF

Department of Radiation Oncology, Boston University Medical Center/School of Medicine, MA 02118-2393, USA.

Most patients received concurrent 5-FU, mitomycin, and radiation. Local control and disease-free/overall survival were determined and analyzed according to patient and treatment parameters. RESULTS: With 43 month median follow-up, projected overall survival is 66% at 5 and 8 years. Disease-free survival is 67% at 5 years and 59% at 8 years. Local control is 70% at 5 and 8 years. Doses of > or =54 Gy are associated with improved 5-year survival (84 vs. 47%, p = 0.02), disease-free survival (74 v. 56%, p = 0.09), and local control (77 vs. 61%, p = 0.04). Although local control, disease-free survival, and overall survival were improved in patients whose overall treatment time was <40 days, this was not statistically significant. Radiation doses of > or =54 Gy are associated with significantly improved survival and local control in anal cancer patients treated with chemoradiation.

J Surg Oncol 1999 Feb;70(2):71-7

30 Gy may be an adequate dose in patients with anal cancer treated with excisional biopsy followed by combined-modality therapy.

Hu K, Minsky BD, Cohen AM, Kelsen DP, Guillem JG, Paty PP, Quan SH

Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.

BACKGROUND AND OBJECTIVES: There are a subset of patients with invasive anal cancers who undergo an excisional biopsy either before or after combined-modality therapy (CMT). The objective of this study is to determine whether these patients can be adequately treated with a lower dose of pelvic radiation therapy. METHODS: A total of 25 patients were treated with CMT either before or after an excisional biopsy. The four subsets included 8 patients with initial excision followed by CMT with 30-34 Gy (EX/30), 6 patients with initial excision followed by CMT with 45-50.4 Gy (EX/45), 10 patients treated by CMT with 30 Gy followed by an excision (30/EX), and 1 patient by CMT with 45 Gy followed by an excision (45/EX). RESULTS: For the total group, the actuarial 5-year disease-free survival was 78%, overall survival was 86%, colostomy-free survival was 91%, and local control was 82%. When patients received CMT either before or following an excision, the actuarial local control and survival results with 30-34 Gy vs. 45-50.4 Gy were similar. In contrast to radiation dose, in patients who received 30-34 Gy, the sequence of the excision (before or after CMT) did appear to have a borderline significant impact on local control. Actuarial 5-year local control was 100% for EX/30 vs. 67% for 30/EX (P = 0.08). CONCLUSIONS: Because of the small number of patients in each group and the retrospective nature of the analysis, it is difficult to draw definitive conclusions from this study. However, our data suggest that in patients who are selected to undergo an initial excisional biopsy followed by CMT, 30 Gy may be an adequate radiation dose. Local control may be higher in patients who undergo an excisional biopsy followed by CMT compared with the converse.

J Clin Oncol 1996 Dec;14(12):3121-5

Primary chemoradiation therapy with fluorouracil and cisplatin for cancer of the anus: results in 35 consecutive patients.

Doci R, Zucali R, La Monica G, Meroni E, Kenda R, Eboli M, Lozza L

Division of Surgery of the Digestive Tract, Istituto Nazionale Tumori, Milan, Italy.

. The treatment protocol consisted of two to three cycles of chemotherapy starting on days 1 and 21 and concurrent radiotherapy at a daily dose of 1.8 Gy up to a total dose of 36 to 38 Gy in 4 weeks, delivered to the anal region, perineum, middle and lower pelvis, and inguinal and external iliac nodes. Radiotherapy was then delivered to the anoperineal region and metastatic inguinal nodes to a total dose of 18 to 24 Gy in 10 fractions. Chemotherapy consisted of 24-hour intravenous (IV) infusion of 5-FU 750 mg/m2 on days 1 to 4 and CDDP 100 mg/m2 by 60-minute IV infusion on day 1. Two patients (6%) had a local recurrence; in one, this was associated with hepatic metastases. One of these patients underwent surgery and is alive after about 4 years, while the other is undergoing chemotherapy. After a median follow-up duration of 37 months, 94% of patients are alive without evidence of disease and 86% are colostomy-free. CONCLUSION: This regimen is well tolerated; its toxicity does not exceed that observed with the combination of 5-FU and mitomycin (MMC). Compared with our previous experience based on the classic CRT (5-FU, MMC, and radiation), the objective response rate observed with this new combination was similar. However, the local recurrence rate, observed in patients treated with the new regimen, was lower (6% v 24%). According to more recent data from the literature, primary CRT is the elective indication in epidermoid cancer of the anus and replacement of MMC with CDDP seems an effective and logical evolution.

Int J Radiat Oncol Biol Phys 1996 Jul 1;35(4):745-9

Initial results of a phase II trial of high dose radiation therapy, 5-fluorouracil, and cisplatin for patients with anal cancer (E4292): an Eastern Cooperative Oncology Group study.

Martenson JA, Lipsitz SR, Wagner H Jr, Kaplan EH, Otteman LA, Schuchter LM, Mansour EG, Talamonti MS, Benson AB 3rd

Mayo Clinic, Rochester, MN 55905, USA.

PURPOSE: A prospective clinical trial was performed to assess the response and toxicity associated with the use of high dose radiation therapy, 5-fluorouracil, and cisplatin in patients with anal cancer. METHODS AND MATERIALS: Patients with anal cancer without distant metastasis were eligible for this study. Radiation therapy consisted of 59.4 Gy in 33 fractions; a 2 week break in treatment was taken after 36 Gy had been given. A treatment of 5-fluorouracil, 1,000 mg/m2 per day intravenously, was given for the first 4 days of radiation therapy, and cisplatin, 75 mg/m2 intravenously, was given on day 1 of radiation therapy. A second course of 5-fluorouracil and cisplatin was given after 36 Gy of radiation, when the radiation therapy was resumed. RESULTS: Nineteen patients entered this study and received treatment. Thirteen (68%) had a complete response, 5 (26%) had a partial response, and 1 (5%) had stable disease. The patient with stable disease and one of the patients with a partial response had complete disappearance of tumor more than 8 weeks after completion of radiation therapy. Fifteen patients had toxicity of Grade 3 or higher: the worst toxicity was Grade 3 in eight patients, Grade 4 in six patients, and Grade 5 in one patient. The most common form of toxicity of Grade 3 or higher was hematologic. The one lethal toxicity was due to pseudomembranous colitis, which was a complication of antibiotic therapy for a urinary tract infection. CONCLUSION. Radiation therapy, cisplatin, and 5-fluorouracil resulted in an overall response rate of 95%. Significant toxicity occurred, an indication that this regimen is near the maximal tolerated dose. A Phase III clinical trial is planned in which radiation therapy, cisplatin, and 5-fluorouracil will be used as an experimental arm.

Int J Radiat Oncol Biol Phys 1999 Apr 1;44(1):127-31

The significance of pretreatment CD4 count on the outcome and treatment tolerance of HIV-positive patients with anal cancer.

Hoffman R, Welton ML, Klencke B, Weinberg V, Krieg R

Department of Radiation Oncology, University of California, San Francisco 94143-0226, USA.

PURPOSE: To assess the outcome and tolerance of HIV-positive patients with anal cancer to standard therapy based on their pretreatment CD4 count. METHODS AND MATERIALS: Between 1991 and 1997, 17 HIV-positive patients with anal cancer and documented pretreatment CD4 counts were treated at the University of California, San Francisco or its affiliated hospitals with either concurrent chemotherapy and radiation or radiation alone. The outcome and complications of treatment were correlated with the patients' pretreatment CD4 count. RESULTS: Disease for all 9 patients with pretreatment CD4 counts > or = 200 was controlled with chemoradiation. Although four required a treatment break of 2 weeks because of toxicity, none required hospitalization. Of the 8 patients with pretreatment CD4 counts < 200, 4 experienced decreased counts, intractable diarrhea, or moist desquamation requiring hospitalization. Additionally, 4 of these 8 ultimately required a colostomy either for a therapy-related complication or for salvage. Nevertheless, 6/7 in this group who received concurrent chemotherapy and radiation had their disease controlled, whereas the patient treated with radiation alone failed and required a colostomy for salvage. CONCLUSION: Patients with CD4 > or = 200 had excellent disease control with acceptable morbidity. Patients with CD4 < 200 had markedly increased morbidity; however, disease was ultimately controlled in 7/8 patients.