Long-term tolerability of fenretinide (4-HPR) in breast cancer patients

Rotmensz, Nicole; Palo, Giuseppe De; Formelli, Franca; Costa, Aurora; Marubini, Ettore; Campa, Tiziana; Crippa, A.; Danesini, Gian Maria; Grottaglie, M. Delle; Mauro, Maria Gaetana Di; Filiberti, A.; Gallazzi, M.; Guzzon, A; Magni, Andrea; Malone, Winfred F.; Mariani, Luigi; Palvarini, M.; Perloff, Marjorie; Pizzichetta, Maria Antonietta; Veronesi, Umberto

doi:10.1016/0277-5379(91)90309-2

Cited by 98 publications

(29 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…20,21 Briefly, eligible patients were <75 years old; operated on for a previously untreated homogeneous or nonhomogeneous oral leukoplakia, with postoperative histology that did not include in situ, miniinvasive or invasive carcinoma; with normal white cell, erythrocyte and platelet counts; and metabolic, renal and liver function tests within 1.5 times upper normal limits. 22,23 Patients were randomized to either no treatment or 4-HPR orally at a dose of 200 mg/day (2 capsules of 100 mg) for 1 year. To allocate a patient, the investigator called the data manager at the Milan coordinating center, who checked inclusion and exclusion criteria and allocated to one of the groups using a randomization list stratified by center.…”

Section: Methodsmentioning

confidence: 99%

Randomized trial of fenretinide (4‐HPR) to prevent recurrences, new localizations and carcinomas in patients operated on for oral leukoplakia: Long‐term results

Chiesa

Tradati

Grigolato

et al. 2005

Intl Journal of Cancer

View full text Add to dashboard Cite

We assessed the efficacy of fenretinide at preventing relapses, new lesions and carcinomas after surgical excision of oral leukoplakia. In a controlled multicenter study, 170 patients operated on for oral leukoplakias with benign postoperative histology were randomized to 200 mg fenretinide daily for 1 year vs. no intervention. Preliminary analysis indicated that fenretinide had good tolerability and was effective at preventing relapses and new lesions during treatment. Analysis after 5-year follow-up suggested that fenretinide protected against relapses and new lesions up to 19 months after randomization, with both limits of the 95% hazard ratio CI for fenretinide vs. control below 1 for 7 months after randomization. There was also a protective effect against all first events, including cancer, for 25 months, with both limits of the 95% CI below 1 up to 11 months after randomization. Subsequently, risk ratio estimates were unstable. Fenretinide was well tolerated and effective at preventing relapses and new leukoplakias during treatment and after. The trial had to be stopped prematurely for very low recruitment and had insufficient power to reveal any protective effect against oral carcinoma; nevertheless, continuing studies on this promising chemopreventive are justified. ' 2005 Wiley-Liss, Inc.

show abstract

Section: Methodsmentioning

confidence: 99%

Randomized trial of fenretinide (4‐HPR) to prevent recurrences, new localizations and carcinomas in patients operated on for oral leukoplakia: Long‐term results

Chiesa

Tradati

Grigolato

et al. 2005

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…The dosage of 4-HPR used in this study was 300 mglday, which is higher than the 200 mglday dosage used in breast cancer prophylaxis studies (24). Although drug levels were not measured in plasma, one can infer, based on the observed toxicity profile in this study, i.e., decreased nocturnal visual acuity, that drug levels were sufficient to achieve a biological effect.…”

Section: Discussionmentioning

confidence: 81%

N‐[4‐hydroxyphenyl] retinamide in rheumatoid arthritis: A pilot study

Gravallese

Händel

Coblyn

et al. 1996

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. To evaluate the efficacy and tolerability of N‐[4 hydroxyphenyl] retinamide (4‐HPR), a synthetic retinoid, in the treatment of rheumatoid arthritis (RA). Methods. An uncontrolled, open clinical trial with synovial biopsy pre‐ and postmedication to evaluate the clinical effects of 4‐HPR as well as its effects on metalloproteinase gene expression. Results. Twelve patients with severe, longstanding RA were enrolled in this study. Six patients withdrew before study completion, 2 because of drug toxicity, 2 because of a flare of RA, and 2 because of intercurrent medical problems. No patient met predetermined Paulus criteria for treatment response, and there was no improvement in the laboratory parameters, except for a modest decrease in C‐reactive protein. No decrease in messenger RNA for the metalloproteinases collagenase and stromelysin was seen in the 2 patients in whom paired synovial biopsies were obtained. Conclusion. No beneficial clinical effect was observed with the retinoid 4‐HPR in the treatment of severe, longstanding RA at the 300 mg/day dosage studied. The use of higher dosages is precluded by the observed toxicities. The effect of this drug in patients with early or mild disease was not studied. Although this particular retinoid was not effective in this pilot study, the use of other retinoids in RA should still be considered.

show abstract

“…14,15 Our study focused on a novel vitamin A derivative that induces apoptosis in a wide variety of malignant cell lines and has been shown to be well tolerated for long durations in large clinical trials. 6,7,[16][17][18][19][20] Previous pilot studies from our group For personal use only. on May 12, 2018. by guest www.bloodjournal.org From demonstrated that 4HPR is superior to other retinoids in inducing growth arrest and apoptosis in human Burkitt lymphoma cell lines in vitro and that it can augment the apoptotic action of anti-CD20 antibodies.…”

Section: Discussionmentioning

confidence: 99%

“…Fenretinide affords a potentially less toxic approach to enhance rituximab's efficacy because it has been found to be well tolerated in a large number of chemopreventive and therapeutic trials. [16][17][18][19][20][34][35][36] Studies using fenretinide doses of up to 400 mg/d orally with a 3-day drug holiday each month demonstrated very low rates (less than 10%) of all toxicities. 17,34,35,37 Such an approach parallels the 2-day-a-week drug holiday that the experimental animals in our study enjoyed.…”

Section: Discussionmentioning

confidence: 99%

Fenretinide enhances rituximab-induced cytotoxicity against B-cell lymphoma xenografts through a caspase-dependent mechanism

Gopal

Pagel

Hedin

et al. 2004

Blood

View full text Add to dashboard Cite

The anti-CD20 monoclonal antibody rituximab induces remission in 40% to 60% of patients with indolent B-cell lymphoma, but virtually all patients have relapses. We evaluated the efficacy of concurrent administration of another biologic agent, N-(4-hydroxyphenyl) retinamide (4HPR, fenretinide) with rituximab against a variety of human B-cell lymphoma cell lines (Ramos, DHL-4, and FL-18) in vivo. Concurrent 4HPR and rituximab administration prevented tumor progression of lymphoma-bearing mice in a minimal disease model (rituximab ؉ 4HPR, 100% progression free; rituximab alone, 37.5% progression free, P ‫؍‬ .01; 4HPR alone, 12.5% progression free, P < .01; controls, 0% progression free, P < .01). Combinations of 4HPR ؉ rituximab exceeded the predicted 50% additive rate of disease control from each agent alone (P ‫؍‬ .038). Administering 4HPR and rituximab to mice with established tumors induced complete responses (CRs) in 80% of animals compared with 20% to 40% CRs using either agent alone (P ‫؍‬ .07), resulting in significantly improved survival. Tumors harvested from 4HPR ؉ rituximab-treated mice displayed elevated caspase activation compared with untreated controls (P ‫؍‬ .02). Adding a broad-spectrum caspase inhibitor in vivo fully abrogated the antitumor effects of 4HPR ؉ rituximab (P ‫؍‬ .05). These results establish the efficacy of 4HPR/rituximab combinations, confirm their caspase-mediated mechanism of action, and offer the potential for disease control with minimal toxicity for patients with B-cell malignancies. (Blood.

show abstract

Long-term tolerability of fenretinide (4-HPR) in breast cancer patients

Cited by 98 publications

References 19 publications

Randomized trial of fenretinide (4‐HPR) to prevent recurrences, new localizations and carcinomas in patients operated on for oral leukoplakia: Long‐term results

Randomized trial of fenretinide (4‐HPR) to prevent recurrences, new localizations and carcinomas in patients operated on for oral leukoplakia: Long‐term results

N‐[4‐hydroxyphenyl] retinamide in rheumatoid arthritis: A pilot study

Fenretinide enhances rituximab-induced cytotoxicity against B-cell lymphoma xenografts through a caspase-dependent mechanism

Contact Info

Product

Resources

About