- Lower doses of IL-2 and 13-cis retinoic acid increased natural “killer” cells.
- Combination therapy might benefit patients with stage 4 cancers.
- Patients who received this combination had improved survival rates.
CHICAGO — Maintenance therapy with interleukin-2 and 13-cis retinoic acid may be an inexpensive method for increasing survival in patients with a variety of stage 4 cancers, according to data reported at the AACR Annual Meeting 2012, held here March 31 – April 4.
Francesco Recchia, M.D., director of oncology at the Civilian Hospital in Avezzano, Italy, started evaluating the maintenance therapy in patients with advanced disease in 1995 after one patient with metastatic melanoma did not tolerate the usual 18 M UI/m2 high-dose interleukin-2 (IL-2) therapy.
“The patient was treated with lower doses, and he had a wonderful, long-lasting response,” he said.
After this observation, Recchia conducted several other studies of IL-2 with or without retinoic acid (RA). “I was encouraged by these preliminary results, and therefore, I conducted a phase II study of this drug combination in 80 patients who had obtained a clinical benefit from chemotherapy. The results were very interesting.”
The researchers evaluated 500 patients with different tumor types, but all with stage 4 disease. After their normal cancer treatment, patients were assigned to self-administered subcutaneous IL-2 (1.8×106 IU) and oral RA (0.5 mg/kg) five days a week for two consecutive cycles of three weeks, followed by a one-week rest, for one year. After a median follow-up of 60 months, researchers reported increased numbers of natural “killer” cells — immune cells with antitumor functions — and a decrease of vascular endothelial growth factor. The 15-year disease-free survival and overall survival rates were 32.6 percent and 36.8 percent, respectively.
“These studies had such good and unexpected results that I thought it would not be ethical to conduct a randomized study without this immunotherapy regimen,” Recchia said. “All types of cancer treated had a benefit from this immunotherapy regimen: ovarian cancer, non-small cell lung cancer, cardiac metastases of sarcoma, colorectal cancer, gastric cancer, renal cell carcinoma, melanoma, head and neck cancer, breast cancer, pancreatic cancer and recurrent ovarian cancer.”
Despite the limitations of different cancer populations, the researchers reported a marked improvement in the five-year overall survival rate for the most commonly treated metastatic cancers compared with National Cancer Institute Surveillance Epidemiology and End Results data: breast (42.7 percent vs. 23.3 percent), lung (26.4 percent vs. 3.6 percent), colorectal (43.6 percent vs. 11.7 percent) and renal (23 percent vs. 11 percent).
Immunotherapy with IL-2 has fallen out of favor in place of newer monoclonal antibodies, according to Recchia. Although his results appear promising, a blinded, controlled, randomized trial would be needed before clinicians could begin using this maintenance regimen.
Press registration for the AACR Annual Meeting 2012 is free to qualified journalists and public information officers: www.aacr.org/PressRegistration .
Follow the AACR on Facebook: http://www.facebook.com/aacr.org 
About the AACR
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR’s membership includes 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 18,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of individual and team science grants in cancer research that have the potential for patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.
For more information about the AACR, visit www.AACR.org .
In Chicago, March 31 – April 4: