A pilot phase II trial of all-trans retinoic acid (Vesanoid) and paclitaxel (Taxol) in patients with recurrent or metastatic breast cancer

• Published in: Investigational new drugs 2011-12, Vol.29 (6), p.1482-1487
• Main Authors: Bryan, Margarette, Pulte, E. Dianne, Toomey, Kathleen C., Pliner, Lillian, Pavlick, Anna C., Saunders, Tracie, Wieder, Robert
• Format: Article
• Language: English
• Subjects: Acids; African Americans; Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Apoptosis; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cancer therapies; Cell death; Clinical trials; Disease Progression; Drug dosages; Estrogens; Female; Hispanic Americans; Humans; Medicine; Medicine & Public Health; Metastasis; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neutropenia; Oncology; Paclitaxel - administration & dosage; Patients; Pharmacology; Pharmacology/Toxicology; Phase II Studies; Pilot Projects; Radiation; Studies; Survival Rate; Toxicity; Treatment Outcome; Tretinoin - administration & dosage
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-010-9478-3

Summary Purpose : We investigated a combination therapy with weekly paclitaxel and all trans -retinoic acid (ATRA) for tolerability, response to treatment, time to progression and survival in previously treated patients with metastatic or recurrent breast cancer. Our rationale was based on preclinical studies demonstrating potentiation of the cytotoxic effects of taxanes and induction of differentiation by ATRA. Patients and methods : Seventeen patients with previously treated metastatic or recurrent breast cancer were enrolled to a regimen of all- trans retinoic acid (Vesanoid, tretinoin, Hoffman-La Roche, Inc.) 45 mg/m 2 PO daily for 4 days starting 2 days before a 1 h treatment with paclitaxel (Taxol, Bristol-Myers Squibb, Plainsboro, NJ) 80 mg/m 2 IV administered weekly for 3 weeks, repeated in 28 day cycles until disease progression or until no longer tolerated. Patients were evaluated for toxicity, response, time to progression and survival. Patients were primarily African American and Latino, representative of the population served by our Cancer Center. Results : The regimen was relatively well tolerated. There were nine grade 3 and one grade 4 toxic events. We administered 162 treatment cycles with a mean of 7.5 per patient (range 1–22, median 5). Three patients had a partial response (17.6%) and ten patients had stable disease (58.8%), with an overall clinical benefit of 76.4%. Median time to progression was 6.0 months (range 1–21, mean 7.7 months). Fourteen evaluable patients had a median survival of 16 months (range 1–68 months, mean 25.2 months). Conclusions : The data suggest this is a well tolerated regimen with modest response rates but with time to progression and survival rates similar to those reported for paclitaxel alone and relatively high rates of stable disease in this sample of patients.