Interferon alfa-2a and 13-cis-retinoic acid in renal cell carcinoma: Antitumor activity in a phase II trial and interactions in vitro Journal Article
| Authors: | Motzer, R. J.; Schwartz, L.; Murray Law, T.; Murphy, B. A.; Hoffman, A. D.; Albino, A. P.; Vlamis, V.; Nanus, D. M. |
| Article Title: | Interferon alfa-2a and 13-cis-retinoic acid in renal cell carcinoma: Antitumor activity in a phase II trial and interactions in vitro |
| Abstract: | Purpose: A phase II trial of interferon alfa-2a (IFN) and 13-cis-retinoic acid (CRA) was conducted in patients with renal cell carcinoma (RCC). In vitro studies were performed to investigate potential mechanisms of interaction. Patients and Methods: Forty-four patients were treated. IFN was given daily at 3 MU and escalated to 6 and 9 MU if tolerated. The dose of CRA was 1 mg/kg/d. The effects of combining CRA and IFN on the proliferation of five RCC cell lines were examined, and retinoid sensitivity was correlated to the expression of retinoic acid receptors. Results: Thirteen (30%) of 43 assessable patients achieved a major response (three complete and 10 partial). Responding sites included bone metastases and renal primary tumors. Seven responding patients remain progression-free at 10+ to 19+ months. The response proportion was higher than in our prior experience with IFN, which was 10% in 149 patients. Eleven of 12 renal cancer cell lines were resistant to CRA alone; one, SK-RC-06, showed 90% inhibition of cell growth. CRA augmented the antiproliferative effect of IFN in several IFN-sensitive cell lines, but not in IFN-resistant lines. Northern blot analysis showed that expression of retinoic acid receptor-β (RAR-β) was repressed and not induced by retinoic acid in retinoic acid-insensitive RCC lines. However, RAR-β expression was induced by retinoic acid in SK-RC-06 cells. Conclusion: IFN and CRA showed antitumor activity in patients with advanced RCC, and the proportion and nature of response suggested CRA added therapeutic benefit to IFN. A phase III randomized trial of IFN plus CRA versus IFN alone and a phase II trial of single-agent CRA have been initiated. |
| Keywords: | adult; clinical article; controlled study; aged; human cell; clinical trial; fatigue; cancer combination chemotherapy; dose response; skin toxicity; bone metastasis; neurotoxicity; anorexia; controlled clinical trial; liver toxicity; phase 2 clinical trial; antineoplastic activity; kidney carcinoma; fever; drug mechanism; xerostomia; isotretinoin; hyperlipidemia; drug formulation; oral drug administration; retinoic acid receptor; recombinant alpha2a interferon; conjunctivitis; subcutaneous drug administration; human; male; female; priority journal; article |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 13 |
| Issue: | 8 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 1995-08-01 |
| Start Page: | 1950 |
| End Page: | 1957 |
| Language: | English |
| DOI: | 10.1200/jco.1995.13.8.1950 |
| PUBMED: | 7636535 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Source: Scopus |
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