Successful Treatment of Anal Carcinoma With Paclitaxel, Cisplatin, and Radiotherapy in a Patient Who Developed a Coronary Syndrome From 5-FU

CASE REPORT

A 55-year-old patient was seen in December 2005 with a history of rectal pain and bright red blood per rectum for 2 months. A colonoscopy showed a 6-cm ulcerated mass at the anorectal junction. Pathology revealed invasive moderately differentiated squamous cell carcinoma (SCC) with no glandular tumor present. A CT scan of the abdomen and pelvis in January 2006 did not reveal any metastatic disease, and the patient was diagnosed as having clinical stage T3 SCC of the anus. The patient was human immunodeficiency virus (HIV) negative, with a carcinoembryonic antigen of 0.9.

Chemoradiotherapy was planned with 5-fluorouracil (5-FU) and cisplatin. The 5-FU was given by continuous infusion over 4 days at a dose of 1000 mg/m², with one dose of cisplatin 60 mg/m². The radiotherapy (RT) was planned to be delivered to the pelvis and inguinal lymph nodes, followed by a cone down to gross disease, with a final cumulative dose of 55.8 Gy in 30 fractions. Treatment was planned using 3-dimensional conformal RT with multileaf collimation.

The patient began the chemoradiotherapy in January 2006 as an inpatient. On day 3, the patient began complaining of severe substernal chest pain. He experienced several episodes of this pain, all of which were relieved by nitroglycerin. A resting electrocardiogram (ECG) revealed normal sinus rhythm with poor R-wave progression in V₂–V₄. Serial troponins were not elevated. A transthoracic echocardiogram was unremarkable. An adenosine stress test demonstrated ECG changes consistent with myocardial ischemia with T-wave abnormalities in V₂–V₄. The patient remained free of chest pain after the 5-FU was discontinued. Cardiology consultants thought that the chest pain had been caused by a 5-FU–induced coronary vasospasm.

We decided to treat the patient with paclitaxel and a lower dose of cisplatin. Paclitaxel 80 mg/m² was given on days 1, 8, and 15, combined with cisplatin 20 mg/m² on days 8 and 15. The patient completed radiation therapy (RT) combined with 3 cycles of paclitaxel and cisplatin in early March 2006.

On follow-up examinations, there has been no evidence of disease. A sigmoidoscopy in August 2006 was normal. Anal canal biopsies were negative 6 weeks and 5 months after treatment. The most recent CT abdomen and pelvis in August 2010 revealed no evidence of recurrence. The patient had normal findings in a colonoscopy and anorectal ultrasound in September 2010. His most recent visit was in April 2011, at which time the physical examination results were normal. It has been more than 5 years since the initial diagnosis, and there is no evidence of recurrence of the disease.

DISCUSSION

We present the case of a patient with anal canal SCC who developed a 5-FU–induced coronary syndrome early in the course of RT. The chemotherapy was changed to paclitaxel and cisplatin, and the patient tolerated the subsequent treatments well. He had a complete pathologic response and continued to be free of disease more than 5 years later. This case shows that paclitaxel and cisplatin can be used with RT in patients with anal cancer who cannot tolerate 5-FU.

SCC of the anal canal can be cured with RT and chemotherapy. The standard treatment regimen was initially developed by Nigro and colleagues.¹ Large cooperative groups have confirmed the activity of this regimen, demonstrating colostomy rates of only 6% to 15% with the use of 5-FU and mitomycin with external beam RT.^2,3 Two large, prospective, randomized trials established the superiority of chemoradiotherapy over RT alone. Arnott et al⁴ compared RT alone to RT with 5-FU and mitomycin and found a benefit in local control of 61% vs. 39%, favoring the chemoradiotherapy arm. The EORTC (European Organization for Research and Treatment of Cancer) 22861 trial compared similar treatment arms and found that combined modality treatment increased local control by 18%.⁵ Most recently, the RTOG (Radiation Therapy Oncology Group) 98-11 phase III trial compared 5-FU, mitomycin, and RT vs. 5-FU and cisplatin with RT and found an improvement in colostomy-free survival in the mitomycin arm.⁶ Our patient was treated before these results were available.

To our knowledge, there has been no documentation in the literature regarding the successful curative management of anal canal SCC with paclitaxel and cisplatin. We suggest that this regimen may be an effective alternative in patients who cannot tolerate 5-FU by continuous infusion.

Paclitaxel has been reported to be active in metastatic anal canal SCC. Alcindor⁷ described 5 patients treated with single-agent paclitaxel for metastatic anal SCC: 2 patients in the first-line setting and 3 patients after initial therapy with cisplatin and 5-FU. Three patients had partial or stable disease, with clinical benefit lasting from 3 to 8 months.⁷

Paclitaxel has been utilized successfully with concurrent RT for other malignancies, including lung cancer. A recent phase III trial of paclitaxel and carboplatin with RT in patients with unresectable non–small-cell lung cancer demonstrated noninferiority and an improved toxicity profile when compared with several other regimens. Both SCC and adenocarcinoma histologies were included in the trial.⁸ A regimen of cisplatin and paclitaxel with RT has been successfully used in the neoadjuvant setting for adenocarcinoma of the gastroesophageal junction.⁹ There are reports from Japan describing the efficacy of paclitaxel as a single agent in the setting of advanced gastric cancer.^10,11

CONCLUSION

Treatment with concurrent RT and paclitaxel has been well described in other malignant diseases, including lung and gastroesophageal cancers. We describe a case of SCC of the anal canal treated with paclitaxel and cisplatin with concurrent RT, in a patient who developed vasospasm from continuous-infusion 5-FU. The patient had a complete response and appeared to be cured more than 5 years later. We believe that this is the first report of the use of this regimen in anal cancer and that consideration should be given to including it in future treatment protocols for SCC of the anus.