Anal cancers (AC) are relatively rare tumors. Their incidence is increasing, particularly among men who have sex with other men due to widespread infection by human papilloma virus. The majority of anal cancers are squamous cell carcinomas, and they are treated according to stage. In local and locally advanced AC, concomitant chemoradiation therapy based on mitomycin C and 5-Fluorouracil (5-FU) is the current best treatment, while metastatic AC, chemotherapy with 5-FU and cisplatin remains the gold standard. There are no indications for induction or maintenance therapies in locally advanced tumors. Many novel strategies, such as targeted therapies, vaccination, immunotherapy and photodynamic therapy are in clinical trials for the treatment of AC, with promising results in some indications.

Anal cancer treatment: Current status and future perspectives

Although successful treatment of squamous cell carcinoma (SCC) of the rectum using chemoradiation therapy (CRT) has been reported, a standard protocol has yet to be established. The aim is to ascertain the effectiveness of CRT with S-1 for three patients with SCC of the rectum. We treated three female patients complaining of rectal bleeding. The patients were diagnosed as having primary SCC of the rectum by means of routine examinations; one of them was a very rare case because of the presence of two lesions in the lower rectum. We treated the patients using CRT with S1 at a radiation dose of 1.8 Gy/fraction given five times weekly (Monday to Friday) to a median dose of 59.4 (45 to 59.4) Gy; S-1 (80 mg/m2/day) was administered orally during radiation therapy. One of three patients had an adverse event involving massive hemorrhage from the tumor. All patients exhibited an excellent response to CRT with S-1; two patients had a complete response, and one patient had a partial response and underwent a posterior pelvic exenteration with advancement flap reconstruction as a salvage treatment. Pathological examination of the resected specimen and lymph nodes revealed no tumor cells indicating a pathological complete response. In this series, the response rate was 100%. We suggest that CRT with S-1 be chosen as the first-line therapy for SCC of the rectum. However, a large study will be required to establish a safe and effective regimen.

/pdf/chemoradiation-therapy-with-s-1-for-primary-squamous-cell-46heucdfaj.pdf

Chemoradiation therapy with S-1 for primary squamous cell carcinoma of the rectum: report of three cases

Background/Aim: S-1 plus cisplatin is the standard first-line chemotherapy for metastatic gastric cancer (MGC) in Japan, but the relationship between dose intensity and antitumor effects remains unclear. Patients and Methods: We retrospectively studied 64 patients who received S-1 plus cisplatin for MGC from January 2006 to December 2010 in two Japanese hospitals. Results: The median relative dose intensity (RDI) of S-1 plus cisplatin was 87% (range, 59.5%-100%). The cut-off value of RDI of S-1 plus cisplatin was identified to be 80% by a receiver operating characteristic analysis of the tumor response. In the RDI<80% (n=19) and the RDI≥80% (n=45) groups, the response rates were 20.0% and 37.5% (p=0.182), the median survival times were 394 and 376 days (p=0.915), and the median progression-free survival (PFS) was 188 and 170 days (p=0.851), respectively. Conclusion: An appropriate RDI reduction may be permitted for patients with MGC in palliative settings. Gastric cancer is the fourth most common malignancy and the second leading cause of related to cancer worldwide death (1). Although several novel chemotherapeutic agents, such as S-1, irinotecan, oxaliplatin, and taxanes, have been shown to be effective against metastatic gastric cancer (MGC), the prognosis of patients with MGC remains poor. Fluoropyrimidine plus cisplatin is generally considered as the standard chemotherapy for MGC worldwide and this combination has been used as a control arm in many phase III clinical trials (2, 3). In a phase III clinical trial for MGC conducted in Japan, S-1 plus cisplatin was recognized as the standard chemotherapy (4). The dose response curve has been shown to be steep and generally linear in highly sensitive types of tumors, such as leukemia, lymphoma, and germ cell tumors, whereas the dose intensity may have little effect in types of relatively insensitive cancer (5). In practice, the doses of anticancer drugs are sometimes reduced for a number of reasons, including adverse events, basal disease and age. However, the appropriate dose reduction to a level that will help retain antitumor activity against MGC remains unclear. Therefore, the present study assessed the relationship between the dose intensity and the antitumor effects of S-1 plus cisplatin chemotherapy against MGC. The results of the present study may provide novel information regarding the management of MGC by using S-1 plus cisplatin chemotherapy.

The relationship between antitumor effects and relative dose intensity of S-1 plus cisplatin treatment for metastatic gastric cancer.

We report a case of anal cancer in a 58-year-old woman who complained of narrow, bloody stools and anal pain. Physical examination revealed anal stenosis associated with a circular mass arising in the anal canal. Histological examination of biopsy specimens confirmed a diagnosis of moderately differentiated squamous cell carcinoma. Enhanced computed tomography revealed anal cancer invading the levator ani and the vagina, with lymph-node, multiple hepatic, and pulmonary metastases. The patient received two cycle of chemoradiotherapy with S-1 plus low-dose cisplatin with rest for 4 weeks, leading to complete response of the primary lesion and a partial response of the metastatic lesions. Each cycle included oral S-1 (120 mg/body; day 1-21), cisplatin (10 mg/body; day 1-5, 8-12) and radiotherapy (2 Gy/day; day 1-5, 8-12, 15-19). Adverse effects of treatment were mild perineal skin erosion and mild appetite loss, but no hematologic toxicity. Although the patient died 16 months after first admission, chemoradiotherapy with S-1 plus cisplatin is potentially effective for the management of advanced anal cancer.

Clinical experience with chemoradiotherapy comprising S-1 plus low-dose cisplatin in a patient with stage IV anal cancer.

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Clinical experience with chemoradiotherapy comprising S-1 plus low-dose cisplatin in a patient with stage IV anal cancer.