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ASCO 2012: Treatment of Anal Cancer in People with HIV

HIV positive people may experience more aggressive anal cancer progression and require prompt diagnosis, researchers reported at the American Society of Clinical Oncology Annual Meeting (ASCO 2012) taking place this week in Chicago. A related study found that quadruple combination anal cancer therapy is safe and may be effective for both HIV positive and negative patients.

As people with HIV live longer due to combination antiretroviral therapy (ART), non-AIDS-defining cancer has become a growing concern.

Anal, cervical, and other genital cancers are caused by oncogenic types of human papillomavirus (HPV). HIV positive people tend to carry more HPV types, are less likely to naturally clear the virus, and may experience more rapid progression from abnormal cells (dysplasia) to pre-cancerous changes (intraepithelial neoplasia) to frank cancer.

Outcomes in Chicago

For HIV negative people, a combination of radiation therapy, 5-fluorouracil (Efudex and other brands), and mitomycin-C has become a standard treatment regimen for non-metastatic invasive anal cancer in HIV negative people, but optimal therapy for HIV positive patients remains undetermined.

Paul Rubinstein from Stroger (Cook County) Hospital in Chicago and colleagues conducted a retrospective analysis of the characteristics and outcomes of 35 HIV positive patients with invasive anal cancer in the County Hospital AIDS Malignancy Project (CHAMP) cohort who were treated with this combination regimen during the past 14 years. Results were compared against a similar cohort of 52 HIV negative patients from the same hospital.

Results

• HIV+ anal cancer patients were younger on average than HIV– patients (44 vs 52 years).
• HIV+ patients were more likely than the HIV– group to be men (89% vs 52%, respectively) and African-American (82% vs 48%, respectively).
• HIV+ and HIV– patients were about equally likely to present with advanced anal cancer, with 45% and 46%, respectively, at Stage IIIA or IIIB; no HIV+ patients presented with Stage IV disease, compared with 15% of HIV– people.
• Time to local recurrence was 20 months shorter, on average, for the HIV+ group.
• The median survival time was similar, 34 months for HIV+ patients compared with 39 months for HIV– (not a significant difference).
• However, no HIV+ patients survived more than 90 months, while 22% of HIV– people survived for 120 months.
• Overall survival did not differ after adjusting for CD4 cell count.

"HIV-associated anal cancer is an African-American male disease compared to HIV– patients in the inner city," the researchers summarized.

"More stage IV disease was reported in the HIV– cohort, but the median survival was equal with no long-term survivors in the HIV+ arm, possibly due to time to local recurrence, which was 20 months shorter, implying more aggressive disease," they continued.

"Both inner city groups present late but tolerate chemotherapy equally well," they concluded. "Education is needed in both HIV+ and HIV– patients to diagnose the cancers early so the overall survival can match the national average."

Quadruple Therapy

In a related presentation, Madhur Garg and fellow investigators with the Eastern Cooperative Oncology Group and the AIDS Malignancy Consortium described Phase 2 trials of a quadruple regimen for anal squamous cell carcinoma consisting of radiation therapy plus the monoclonal antibody cetuximab (Erbitux, an epidermal growth factor receptor inhibitor) plus cisplatin (a platinum drug) plus 5-fluorouracil.

Study AMC045 included HV+ patients, while Study ECOG 3205 included HIV– patients with normal immune function. The researchers presented complete safety data for both trials; the efficacy data included 45 patients from AMC045 the first 28 patients from E3205.

Results

• Among the 45 HIV+ patients, 24% had Stage I anal cancer, 42% had Stage II, and 34% had stage III.
• Among the 28 HIV– people, the corresponding rates were 11%, 50%, and 39%.
• 37 HIV+ patients (82%) and 22 HIV– patients (79%) competed the treatment protocol.
• Type I or II immunological adverse events were uncommon, occurring in 4% of HIV+ and 8% of HIV– patients.
• 7% of HIV+ and 14% of HIV– patients underwent colostomies.
• 2-year progression free survival rates were 80% for the HIV+ group and 92% for the HIV– group.
• 2-year overall survival rates were similar, at 89% and 93%, respectively.

The quadruple regimen "is feasible in patients with squamous cell carcinoma of the anal canal including patients with HIV infection," the researchers concluded. While "p]reliminary safety and efficacy data appear encouraging," they emphasized that additional follow-up is needed to determine efficacy.

6/5/12

References

PGRubinstein, SB Sreenivasappa, S Gupta, et al. Concurrent chemoradiotherapy with 5-fluorouracil and mitomycin-C for invasive anal carcinoma in HIV-positive patients receiving highly active anti-retroviral therapy versus non-HIV patients. American Society of Clinical Oncology Annual Meeting (ASCO 2012). Chicago, June 1-5, 2012. Journal of Clinical Oncology 30 (supplement). Abstract e14590.

M Garg, JY Lee, LA Kachnic, et al. Phase II trials of cetuximab (CX) plus cisplatin (CDDP), 5-fluorouracil (5-FU) and radiation (RT) in immunocompetent (ECOG 3205) and HIV-positive (AMC045) patients with squamous cell carcinoma of the anal canal (SCAC): Safety and preliminary efficacy results. American Society of Clinical Oncology Annual Meeting (ASCO 2012). Chicago, June 1-5, 2012. Journal of Clinical Oncology 30 (supplement). Abstract 4030.