Standard of Care for Anal Cancer Should Not Be Changed

Findings from the largest trial ever conducted for anal cancer have shown that the current standard of care, using a novel, continuous radiation therapy delivery program combined with 5-fluorouracil (5-FU) , (a drug commonly used to treat many types of cancer including, breast, head and neck, anal, stomach, colon and some skin cancers), and mitomycin-C (a chemotherapy drug mainly used to treat bladder and rectal cancers, but also sometimes pancreatic, lung and breast cancers), results in the best outcomes so far reported for patients with anal cancer, and that cisplatin chemotherapy (a drug approved to be used together with other drugs to treat many different cancers), is not superior to mitomycin-C.

The study, presented on Saturday, May 30, 2009 by Roger James, MD, Maidstone Hospital, Kent, UK, during the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO) being held from May 27 – June 2, 2009 in Orlando, Florida, also showed no evidence of a benefit of adding maintenance chemotherapy to the standard of care.

Anal cancer is rare, with about 5,000 patients diagnosed in the United States each year. In the United Kingdom about 850 people are diagnosed with this disease each year. It is slightly more common in women than men, with rates increasing in women over the past 10 years.

Unlike colorectal cancer, the majority of patients with anal cancer do not need surgery, largely because the tumors are the squamous cell type, which are very responsive to chemotherapy and radiation. Cisplatin is commonly used for other squamous cell cancers, but it is less convenient to deliver and is known to have different toxicities from mitomycin-C, such as neurological and renal side effects and hearing loss.

The current study, called ACT II, conducted by the National Cancer Research Institute in the United Kingdom, and funded by Cancer Research UK, randomized 940 patients to receive radiation therapy given at the same time as 5-FU with either mitomycin-C or cisplatin. Patients were also randomized to receive follow-up maintenance therapy with cisplatin and 5-FU after chemoradiation or no maintenance therapy.

After a median follow-up of three years, the investigators found no significant difference in outcome in the two randomized comparisons:

• The complete response rate at 6 months (the number of patients who had all signs of their cancer disappear) was 94 percent in the mitomycin-C group compared with 95 percent in the cisplatin group.
• Recurrence-free survival at 3 years (the number of patients whose tumors did not return) was 75 percent both in patients who got maintenance therapy and in those who did not.
• Overall survival at 3 years was 85 percent in patients who received maintenance therapy and 84 percent in those who did not.

“These findings are good news in spite of the lack of evidence for an improvement in giving either cisplatin or maintenance therapy, since the standard chemoradiation schedule given in this trial was highly effective,” said Roger James, MD, FRCP, FRCR, a radiation oncologist from Maidstone Hospital, Kent, United Kingdom, and the study’s lead author. “Although this trial did not show an improvement from adding maintenance therapy, some form of additional treatment will be the subject of future studies, to determine whether some subset of patients might benefit from it.”

For more information:

• The National Cancer Research Institute (NCRI)
• Cancer Research UK
• Anal Cancer trials (UK)
• Glynne-Jones R, Mawdsley S, Anal Cancer: The End of the Road for Neoadjuvant Chemoradiotherapy? Journal of Clinical Oncology (JCO), Vol 26, No 22 (August 1), 2008: pp. 3669-3671

2009 ASCO Annual Meeting Abstracts:

• James R, Wan S, Glynne-Jones R, Sebag-Montefiore D, Kadalayil L, Northover J, Cunningham D, Meadows M, Ledermann J, National Cancer Research Institute (NCRI) ACT II Trial Management Group. A randomised trial of chemoradiation using mitomycin or cisplatin, with or without maintenance cisplatin/5FU in squamous cell carcinoma of the anus (ACT II) LBA4009

Illustration courtesy of the American Society of Clinical Oncology.