Abstract
13-cis-retinoic acid (isotretinoin) and interferon-α have limited activity as single agents in advanced cancer. Preclinical data indicate that these agents have different mechanisms of action and, in combination have greater activity (that is, the ability to modulate growth and differentiation) in a number of malignant cell types than either agent alone. In clinical trials, the new biological regimen of 13-cis-retinoic acid and interferon-α was shown to have major activity in advanced squamous cell carcinoma of the skin and cervix. We conducted a phase II trial of this regimen in recurrent squamous cell carcinoma of the head and neck. Of the 21 evaluable patients, none had a complete response, and only one had a partial response (5%). Two patients had minor responses, four had stable disease, and 14 experienced disease progression. Five patients developed grade 3 toxic effects, including skin toxicity, fatigue, headache, and anorexia/weight loss. The median survival duration was 25.5 weeks (range, 4–95). The combination of 13-cis- retinoic acid and interferon-α at this dose and schedule is ineffective for the treatment of recurrent squamous cell carcinoma of the head and neck.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Boring CC, Squires TS, Tong T: Cancer statistics, 1992. CA 42:19–38, 1992
Wolf G, Lippman SM, Laramore G, Hong WK: Head and Neck Cancer. In: Holland JF, Frei E, Bast RC Jr, Kufe DW, Morton DL, Weichselbaum R (eds) Cancer Medicine, 3rd ed. Philadelphia, Lea & Febiger (in press)
Lippman SM, Kessler JF, Meyskens FL Jr: Retinoids as preventive and therapeutic anticancer agents. Cancer Treat Rep 71:391–405, 493–515, 1987
Lippman SM, Kessler JF, Al-Sarraf M, Alberts DS, Itri LM, Mattox D, Von Hoff DD, Loescher L, Meyskens FL: Treatment of advanced squamous cell carcinoma of the head and neck with Isotretinoin: A phase-II randomized trial. Invest New Drugs 6:51–56, 1988
Smith MA, Parkinson DR, Cheson BD, Friedman MA: Retinoids in cancer therapy. J Clin Oncol 10:839–864, 1992
Medenica R, Slack N: Clinical results of leukocyte interferon-induced tumor regression in resistant human metastatic cancer resistant to chemotherapy and/or radiotherapy-pulse therapy schedule. Cancer Drug Delivery 2: 53–75, 1985
Fierro R, Johnson J, Myers E, Colao D, Pelch K, Rust D, Wagner R, Whiteside T, Vlock D: Phase-II trial of nonrecombinant interferon-α (IFN) in recurrent squamous cell carcinoma of the head and neck SCCHN (Abstract). Proc Am Soc Clin Oncol 7:156, 1988
Miyake H, Horiuchi M, Togawa K, Kawamoto K, Kaneko T, Inuyama Y, Honda Y, Baba S, Matsunaga T, Ishikawa T: Recombinant interferon-α 2a (SCH 30500) in patients with head and neck cancer. Gan To Kogaku Ryoho 12: 1651–1655, 1985
Hong WK, Endicott J, Itri LM, Doos W, Batsakis JG, Bell R, Fofonoff S, Byers R, Atkinson EN, Vaughn C: 13-cis- Retinoic acid in the treatment of oral leukoplakia. N Engl J Med 315:1501–1505, 1986
Hong WK, Lippman SM, Itri LM, Karp DD, Lee JS, Byers RM, Schantz SP, Kramer AM, Lotan R, Peters LJ: Prevention of second primary tumors with isotretinoin in squamous cell carcinoma of the head and neck. N Engl J Med 323: 795–801, 1990
Hemmi H, Breitman TR: Combination human interferon and retinoic acid synergistically induced differentiation of the human promyelocytic leukemia cell line HL-60. Blood 69:501–507, 1987
Frey JR, Peck R, Bollag W: Antiproliferative activity of retinoids, interferon-α and combination in five human transformed cell lines. Cancer Lett 57:223–227, 1992
Higuchi T, Hannigan GE, Malkin D, Yeger H, Williams BR: Enhancement by retinoic acid and dibutyryl cyclic adenosine 3′ 5′ -monophosphate of the differentiation and gene expression of neuroblastoma cell induced by interferon. Cancer Res 51:3958–3964, 1991
Borden EC: Interferons — expanding therapeutic roles. N Engl J Med 326:1491–1493, 1992
Dmitrovsky E, Bosl GJ: Active cancer therapy combining 13-cis-retinoic acid with interferon-α. J Natl Cancer Inst 84:218–219, 1992
Lippman SM, Parkinson DR, Itri LM, Weber RS, Schantz SP, Ota DM, Schusterman MA, Krakoff IH, Gutterman JU, Hong WK: 13-cis-Retinoic acid and interferon-α 2a: Effective combination therapy for advanced squamous cell carcinoma of the skin. J Natl Cancer Inst 84:235–241, 1992
Lippman SM, Kavanagh JJ, Paredes-Espinoza M, Delgadillo-Madrueno F, Paredes-Casillas P, Hong WK, Holdener E, Krakoff IH: 13-cis-retinoic acid plus interferon alpha-2a: High activity systemic therapy for squamous cell carcinoma of the cervix. J Natl Cancer Inst 84:241–245, 1992
Ajani JA, Welch SR, Raber MN, Fields WS, Krakoff IH: Comprehensive criteria for assessing therapy-induced toxicity. Cancer Invest 8:147–159, 1990
Kinsella TJ, Gould MN, Mulcahy RT, Ritter MA, Fowler JF: Integration of cytostatic agents and radiation therapy: A different approach to “proliferating” human tumors. Int J Radiat Oncol Biol Phys 20:295–302, 1991
Rutz HP, Little JB: Modification of radiosensitivity and recovery from X ray damagein vitro by retinoic acid. Int J Radiat Oncol Biol Phys 16:1285–1288, 1989
Torrisi J, Berg C, Bonnem E, Dritschilo A: The combined use of interferon and radiotherapy in cancer management. Semin Oncol 13(Suppl 2):78–83, 1986
Wadler S, Schwartz EL: Antineoplastic activity of the combination of interferon and cytotoxic agents against experimental and human malignancies: A review. Cancer Res 50:3473–3486, 1990
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Voravud, N., Lippman, S.M., Weber, R.S. et al. Phase II trial of 13-cis-retinoic acid plus interferon-α in recurrent head and neck cancer. Invest New Drugs 11, 57–60 (1993). https://doi.org/10.1007/BF00873912
Issue Date:
DOI: https://doi.org/10.1007/BF00873912