Mitomycin, 5-fluorouracil, and radiotherapy for anal canal cancer in a patient undergoing hemodialysis: a case report

Change history

11/21/2025

The original online version of this article was revised: the article title has been corrected.

Abstract

Anal cancer is a rare malignancy that accounts for only 0.3% of all cancer cases. Clinical data on treatment strategies for patients with special conditions, such as impaired renal function or those undergoing dialysis, are limited. Herein, we report a case highlighting the efficacy and safety of a combination regimen of mitomycin C (MMC), 5-fluorouracil (5-FU), and radiotherapy (RT) in a patient undergoing dialysis. A 65 year-old woman undergoing hemodialysis three times per week for chronic kidney disease associated with polycystic kidney disease presented with hematochezia. Biopsy confirmed human papillomavirus (HPV)-related anal squamous cell carcinoma, clinical stage cT1N0M0 (Stage I). The patient underwent two cycles of MMC and 5-FU combined with RT. The adverse events included grade 3 neutropenia, grade 3 thrombocytopenia, grade 2 nausea, grade 1 vomiting, and grade 3 diarrhea. Post-treatment endoscopic and histological evaluations confirmed a complete response. This case suggests that MMC + 5-FU + RT may be a viable treatment option with manageable toxicity, even in patients with anal canal cancer undergoing dialysis.

Introduction

Anal cancer is a rare malignancy, accounting for only 0.3% of all cancers, with an estimated 50,865 new cases reported worldwide in 2020 [1]. Anal cancer is classified as anal canal cancer or perianal cancer. Given the high radiosensitivity of anal canal cancer and the goal of preserving the anal sphincter, radiation therapy is prioritized over surgery as local treatment. Chemoradiotherapy (CRT), which combines radiation therapy with systemic chemotherapy, is the standard treatment. The most commonly used chemotherapeutic agents are mitomycin C (MMC) and 5-fluorouracil (5-FU). For anal cancer, in general, CRT has been shown to reduce local recurrence rates and improve overall survival compared with radiation therapy alone [2].

Owing to the rarity of anal canal cancer, there are limited clinical data regarding special populations, such as those with significantly impaired renal function, who are often excluded from clinical trials. Since the primary routes of excretion of MMC and 5-FU are not renal, some reports suggest that dose adjustments are unnecessary in patients with renal impairment [3, 4]. However, other reports advise against the use of MMC in patients with a glomerular filtration rate < 30 mL/min or those undergoing dialysis and recommend a 33–50% dose reduction of 5-FU in patients with renal dysfunction [5]. Thus, indications for appropriate dosing of MMC and 5-FU in patients with renal impairment, including those receiving dialysis, remain inconsistent and poorly defined.

The 5-year survival rate of patients with localized anal canal cancer treated with CRT is relatively favorable, ranging from 76.0% to 78.3% for T2–T4N0–3 disease [6, 7], and reaching 86.6% for early-stage T1–T2N0 disease [8]. Therefore, even in dialysis patients who are at an increased risk of treatment-related adverse events, curative CRT may still be a worthwhile option, depending on the disease stage.

Here, we report a case of anal canal cancer in a dialysis patient who was successfully treated with MMC + 5-FU + RT and achieved a complete response. To the best of our knowledge, this is the first report to describe the efficacy and safety of CRT with MMC and 5-FU in patients undergoing dialysis.

This case report was prepared according to the CARE Guidelines [9].

Case report

In Year X and Month X, the patient presented to another hospital with a chief complaint of massive hematochezia. Sigmoidoscopy revealed thrombosed internal hemorrhoids. As the bleeding persisted the following day, the patient visited our hospital for further evaluation, and a colonoscopy was performed (Fig. 1). Examination revealed the rupture of the thrombosed internal hemorrhoid. One week later, the bleeding resolved spontaneously, leaving behind induration. In Year X, Month X + 3, an anorectal examination showed a thumb-sized induration at the 9 o’clock position, with no signs of improvement. A biopsy was performed, and based on the histological findings, the patient was diagnosed with HPV-related anal squamous cell carcinoma (cT1N0M0 stage I). The patient was admitted to our hospital for treatment.

Fig. 1.

Endoscopic findings at emergency admission

The patient was a 65-year-old woman with comorbid hypertension and renal dysfunction due to polycystic kidney disease, who required hemodialysis three times per week (Monday, Wednesday, and Friday). The patient’s regular medications included evocalcet 2 mg/day, alfacalcidol 0.5 μg/day, olmesartan 40 mg/day, cilnidipine 20 mg/day, carvedilol 8 mg/day, lanthanum carbonate 750 mg/day, clotiazepam 15 mg/day, maprotiline 10 mg/day, a lactic acid bacteria preparation (Biofermin) 3 tablets/day, and daikenchuto (a traditional Japanese Kampo medicine) 7.5 g/day. The patient had no history of allergic reactions or adverse drug events.

CRT for anal canal cancer was initiated in Month X + 3, consisting of MMC 10 mg/m² on day 1 and 5-FU 1000 mg/m² on days 1–4. Both doses were reduced to 80% and administered in 28 day cycles for two cycles (Fig. 2). RT was planned at 59.4 Gy in 33 fractions. The overall treatment course is shown in the timeline (Fig. 3).

Fig. 2.

Chemotherapy regimen. DEX dexamethasone, MMC mitomycin C, 5-FU 5-fluorouracil, APR aprepitant

Fig. 3.

Changes in hematologic toxicity during chemotherapy. MMC mitomycin C, 5-FU 5-fluorouracil

During the first cycle, the patient experienced grade 1 nausea and vomiting on days 4–6, which were managed with metoclopramide 5 mg and olanzapine 5 mg. On day 9, grade 3 neutropenia (neutrophil count: 576/μL) and grade 1 thrombocytopenia (platelet count: 82,000/μL) developed. Filgrastim (75 μg/day) was initiated. By day 11, neutrophils had recovered to 2800/μL, and filgrastim was discontinued. On day 18, neutrophil count remained stable at 2236/μL, but thrombocytopenia worsened to grade 3 (49,000/μL on day 11 and 28,000/μL on day 18). From day 24, grade 1 radiation dermatitis was observed in the anal region, which progressed to grade 2 radiation dermatitis with erosions by day 32. On the scheduled start day for the second chemotherapy cycle (day 29), grade 3 neutropenia (600/μL) recurred, leading to treatment delay and re-initiation of filgrastim. Neutrophils recovered to 2240/μL by day 32, and the second cycle of MMC + 5-FU began on day 35. Due to adverse events in the first cycle, the doses of MMC and 5-FU were further reduced to 70% in the second cycle. To improve antiemetic control and to avoid the constipating effects of 5-hydroxytryptamine 3 receptor antagonists due to the patient’s pre-existing anal cancer-related constipation, aprepitant was added (125 mg on day 1 and 80 mg/day on days 2–3) along with dexamethasone (8 mg/day on days 2–4). In the second cycle, the minimum neutrophil count was 1292/μL, and the minimum platelet count was 96,000/μL. Nausea or vomiting was not observed. Grade 3 diarrhea occurred on days 9–12 but was relieved with as-needed loperamide (1 mg). The patient completed treatment and was discharged on day 60 (Month X + 5).

In Month X + 6, a post-CRT colonoscopy was performed. A complete response (CR) was assessed based on qualitative evaluation (Fig. 4). A post-CRT scar of a known anal squamous cell carcinoma is observed above the dentate line. Although most of the lesions were scarred, some remained ulcerated, and the base was blackish. Histopathological examination of biopsies from the five sites revealed no atypical cells. At Month X + 7, CT confirmed no evidence of distant metastasis or recurrence. In Month X + 9, a second colonoscopy showed no malignancy on two additional biopsies from the scar site. In Year X + 1, Month X, the second post-CRT CT scan confirmed the absence of distant recurrence. CR was maintained. Careful surveillance is ongoing after CRT.

Fig. 4.

Endoscopic findings at the time of complete response evaluation

Discussion

To our knowledge, this is the first reported case documenting the clinical course of MMC + 5-FU + RT therapy in a patient with anal canal cancer undergoing hemodialysis. With the aging population, the incidence of both cancer and chronic kidney disease is increasing [10], making the coexistence of these conditions increasingly common. Optimal drug efficacy and minimal adverse effects require careful dose adjustments and appropriate timing relative to dialysis sessions [11]. This case provides valuable insights for decision-making in clinical scenarios.

The CRT regimen used in this case—MMC 10 mg/m² on day 1, 5-FU 1000 mg/m² over 96 h on days 1–4, and 59.4 Gy/33 fractions—was based on protocols from major clinical trials [6, 7]. In this patient, the first cycle was administered at 80% of the standard dose; owing to bone marrow suppression, the second cycle was further reduced to 70% with both agents. There are no established guidelines for dose adjustment of MMC or 5-FU in patients with renal dysfunction, and some reports suggest that no dose reduction is needed [3, 4]. However, in this case, the initial dose reduction may have helped to avoid severe toxicity. The patient underwent dialysis three times a week (Monday, Wednesday, and Friday), starting at 9:00 AM. However, data on the dialyzability of MMC are limited. MMC has an albumin-binding rate of 8.4–12.8%, a half-life of 32.9–50.2 min, and a volume of distribution of 23.0–32.2 L/m² (based on the Japanese drug label). Its low binding rate suggests that it may be removed by dialysis, but its rapid tissue distribution may minimize the effects of dialysis, depending on the timing. In this case, MMC was administered post-dialysis or on non-dialysis days, suggesting little impact of dialysis. 5-FU is known to be approximately 80% dialyzable [12]. Given the 4 h duration of each dialysis session, 5-FU was partially removed during approximately 8 of the total 96 h of infusion. The first cycle involved a reduced dose of 800 mg/m² per day (total: 3200 mg/m²). It is estimated that approximately 3000 mg/m² (75%) remains in the body, and the dialysis-related reduction is only approximately 5%.

During the first cycle, the patient experienced grade 2 nausea, grade 1 vomiting, grade 3 neutropenia, and grade 2 thrombocytopenia. According to clinical trial data, grade ≥ 3 myelosuppression occurs in 61.4%, and grade ≥ 2 nausea in 25% of patients undergoing MMC + 5-FU + RT [4], indicating that the adverse events in this case were within expected ranges. In the second cycle, dose reductions and stronger antiemetic prophylaxis resulted in manageable toxicity, with no nausea or vomiting and ≤ grade 2 myelosuppression, demonstrating good tolerability of MMC + 5-FU + RT in this patient.

The CR was assessed based on endoscopic and pathological findings. In a phase II clinical trial using the same regimen, the CR rate was 88% [7], suggesting that active treatment should be considered, even for patients on dialysis. A study conducted in Japanese patients reported favorable outcomes with a modified regimen in which the 5-FU dose was reduced to 800 mg/m², achieving a CR rate of 87.1% and a 2 year survival rate of 93.5% [13]. Although a CR was achieved in the present case by using a dose-reduced version of the global standard regimen, good treatment outcomes have been demonstrated with dose-reduced regimens in the Japanese population. Therefore, these findings should be interpreted with caution, particularly given that the patient was Japanese.

The limitations of this case report include the short observation period of 1 year from diagnosis and the limited evaluation with CT imaging due to the presence of multiple renal cysts.

Conclusion

This case suggests that MMC + 5-FU + RT therapy can be manageable toxicity in patients with anal canal cancer undergoing hemodialysis, supporting the feasibility of active treatment in such cases.

Ethical approval

Ethics committee approval was not required.

Informed consent

Written informed consent was obtained from patient for this case report.

Author contributions

YO was the main author of the project and wrote the first draft of the manuscript. MM contributed to the anal canal cancer treatment. JK and RY contributed to this study from a pharmacological perspective. All authors reviewed and edited the manuscript, and approved the final version.

Funding

The authors received no financial support.

Data availability

The data supporting this study’s findings are available from the corresponding author upon reasonable request.

Declarations

Conflict of interest

The authors declare no potential conflicts of interest.