ASCO 2009-STANDARD OF CARE FOR ANAL CANCER SHOULD NOT BE CHANGED

May 31, 2009 (Orlando, Florida) — A phase 3 study has demonstrated that the current standard of care for anal cancer should not be changed. According to results from the largest trial to date conducted for anal cancer, cisplatin chemotherapy is not superior to the standard of care in the treatment of anal cancer.

The study, presented here at the American Society of Clinical Oncology 45th Annual Meeting, also found that there was no benefit to adding maintenance therapy to standard care.

"Most of these are squamous cell carcinomas, and they are highly sensitive to radiotherapy and chemotherapy," said lead author Roger James, MD, FRCP, FRCR, a radiation oncologist from Maidstone Hospital in Kent, United Kingdom. "The standard treatment was established by 3 large clinical trials that were conducted during the 1990s."

Chemoradiotherapy with 5-fluorouracil (5-FU) and mitomycin-C is currently the standard treatment for anal cancer. Squamous cell carcinoma of the anal canal has historically been treated with abdominoperineal resection, but chemoradiation has been shown to result in high rates of local control and disease-free and colostomy-free survival without surgery. For patients who fail this regimen, explained Dr. James, surgery might then be indicated.

Anal cancer is relatively rare, with only about 5000 cases diagnosed in the United States each year. However, unlike colorectal cancer, the majority of patients with anal cancer do not require surgery since the tumors are generally very responsive to chemoradiation.

"Our major end point was complete response rate," said Dr. James. "There was no difference at the end of the trial [after] adding cisplatin."

The goal of the ACT II trial, conducted by the National Cancer Research Institute in the United Kingdom, was to address 2 research questions, explained Dr. James. The first was to evaluate whether replacing mitomycin-C with cisplatin would improve the complete response rate; the second was to evaluate whether adding 2 cycles of maintenance chemotherapy with 5-FU and cisplatin, after chemoradiation, would reduce disease recurrence.

The researchers randomized 940 patients to chemoradiation with either mitomycin-C or cisplatin. All patients received 5-FU (1000 mg/m² per day on days 1 to 4 and days 29 to 32) and radiotherapy (50.4 Gy in 28 fractions), and were then randomized to receive either mitomycin-C (12 mg/m² on day 1; n = 471) or cisplatin (60 mg/m² on days 1 and 29; n = 469).

The cohort was also randomized to receive maintenance therapy (n = 448) 4 weeks after chemoradiation with 2 cycles of cisplatin and 5-FU in weeks 11 and 14, or no maintenance therapy (n = 446).

Clinical response was assessed at 11 and 18 weeks, and patients underwent a computed tomography scan at 26 weeks. At a median follow-up of 2.5 years, investigators found no significant difference in outcomes between the 2 groups. The complete response rate at 6 months was 94% in the mitomycin-C group and 95% in the cisplatin group.

At 3 years, the researchers did not find a difference between patients who received maintenance therapy and those who did not. Recurrence-free survival was 75% in both study groups, and overall survival was 85% in patients who received maintenance therapy and 84% in those who did not.

Toxicity profiles differed among patients who received mitomycin-C and those who received cisplatin. Although the rates of nonhematological toxicities were similar in the 2 study groups, patients who received cisplatin had fewer acute grade 3/4 hematological toxicities (12% vs 25%; P < .001).

"ACT II did not show any significant differences between cisplatin and mitomycin-C," Dr. James said, adding that very high response rates and excellent tolerability can be achieved with this chemoradiotherapy schedule.

Nicholas Petrelli, MD, medical director of the Helen F. Graham Cancer Center in Wilmington, Delaware, who was approached by Medscape Oncology for independent comment, pointed out that "this is a good negative trial."

"It was a well-designed study, and it demonstrates that the standard of care is very effective," said Dr. Petrelli. "In the 1980s, the treatment was surgery, and patients ended up with a colostomy. . . The results of Dr. James' study — they are very good and hard to surpass."

American Society of Clinical Oncology (ASCO) 45th Annual Meeting: Abstract LBA4009. Presented May 30, 2009. Abstract