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NCI 6896: a phase I trial of vorinostat (SAHA) and isotretinoin (13-cis retinoic acid) in the treatment of patients with advanced renal cell carcinoma.

TitleNCI 6896: a phase I trial of vorinostat (SAHA) and isotretinoin (13-cis retinoic acid) in the treatment of patients with advanced renal cell carcinoma.
Publication TypeJournal Article
Year of Publication2020
AuthorsMolina AM, van der Mijn JC, Christos P, Wright J, Thomas C, Dutcher JP, Nanus DM, Tagawa ST, Gudas LJ
JournalInvest New Drugs
Date Published2020 Jan 03
ISSN1573-0646
Abstract

Preclinical studies suggest that histone deacetylase (HDAC) inhibitors may restore tumor sensitivity to retinoids and have synergistic anti-tumor activity when combined. We performed a Phase I clinical trial to evaluate the safety and preliminary efficacy of combining the oral HDAC inhibitor vorinostat and isotretinoin in patients with advanced renal cell carcinoma (RCC). Vorinostat was administered at 300 mg orally twice daily in combination with escalating doses of isotretinoin for 3 consecutive days per week. A standard 3 + 3 dose escalation design was used. Dose limiting toxicities (DLT) were assess during the first cycle to determine the maximum tolerated dose (MTD). Fourteen patients enrolled on the trial of which 12 were evaluable for toxicity (6 cohort 1; 3 cohort 2; 3 cohort 3) and 11 for tumor response. One patient in cohort 1 experienced a DLT (grade 3 depression). Common grade 1-2 toxicities included fatigue and GI effects (nausea, diarrhea, anorexia). MTD was established as vorinostat 300 mg with isoretinoin 0.5 mg/kg twice daily 3 days per week. Best responses in evaluable patients included 1 partial response and 9 stable disease, lasting a median of 3.7 months (range 1.8-10.4 months). The combination of vorinostat and isotretinoin is safe, tolerable and associated with responses in patients with refractory metastatic RCC.

DOI10.1007/s10637-019-00880-7
Alternate JournalInvest New Drugs
PubMed ID31898184
Grant ListNO1-CM-62204 / / New York Cancer Consortium /
N/A / / CTEP-NCI /
N/A / / Turobiner Cancer Research Fund /
Division: 
Biostatistics
Category: 
Faculty Publication