Interferon Alfa-2a en isotretinoin plus vitamine E. verbeteren significant - verdubbeling overlevingskansen en overlevingstijd na 5 jaar van patienten met kanker in mond en keel na operatie

20 april 2005: Bron: Arch Otolaryngol Head Neck Surg. 2005;131:304-307 en Medscape

Een combinatie van Interferon Alfa-2a, Isotretinoin, plus Vitamin E gegeven na operatie verhoogt hoog significant de kansen op overleving van mond- en keelkanker en vergroot significant de tijd tot een recidief en verdere uitzaaiïngen, aldus een weliswaar niet-gerandomiseerde fase II studie bij 45 patiënten, maar wel vergeleken bij wat statistisch mocht worden verwacht bij deze patiënten. Deze studie is nieuwe bevestiging van deze effectieve aanpak als resultaat uit een studie uit 2001, zie ander bericht onder voeding en voedingstoffen en effect bij mond- en keelkanker.

Vijf jaar ziektevrije overleving was 80% (95% confidence interval , 65.1% - 89.1%), en uiteindelijk definitieve overleving van deze groep was 81,3% (95% CI, 63.7% - 90.9%). Deze resultaten zijn hoog significant beter - verdubbeling - dan de historische vijfjaars cijfers voor gevorderde = met utizaaiëngen - mond- en keelkanker welke mediaan staat op ca. 40%. Let wel een verdubbeling van de overlevingscijfers met slechts enkele extra voedingssupplementen, die ook nog eens de toxiciteit tegengaan. Dit betekent dat van elke twee patiënten die nu nog een recidief krijgt en sterft binnen vijf jaar er met deze aanpak 1 definitief geneest en minimaal vijf jaar ziektevrij blijft na operatie.

Interferon Alfa-2a, Isotretinoin, Plus Vitamin E May Improve Survival in Head/Neck Cancer

Laurie Barclay, MD
April 18, 2005 — The bioadjuvant combination of interferon alfa-2a, isotretinoin, and vitamin E improves survival for patients with squamous cell carcinoma of the head and neck (SCCHN), according to the results of a long-term follow-up of a phase 2 trial published in the April issue of the Archives of Otolaryngology – Head & Neck Surgery.

"Despite advanced curative therapy for SCCHN, the outcome of such treatment is poor," write Jose A. Seixas-Silva, Jr., MD, from the University of Pittsburgh Cancer Institute in Pennsylvania, and colleagues. "Preventive strategies are clearly desirable. Retinoids, including vitamin A and its synthetic derivatives, have been extensively studied during the past two decades."

In this phase 2 prospective study carried out at tertiary care academic medical centers, all 45 participants had stage III or IV SCCHN and had been treated with surgical resection, radiation, or both. Median age was 52 years. All patients were then treated for 12 months with bioadjuvant chemopreventive treatment consisting of isotretinoin, interferon alfa-2a, and vitamin E.

The authors previously reported a 24-month median follow-up of this phase 2 trial of combination bioadjuvant therapy after definitive local therapy. Although all 45 patients completed treatment, one patient was excluded from analysis of recurrence and development of second primary tumors. The primary outcome in this report was longer-term follow-up (median, 49.4 months).

Of the 45 patients, seven patients (16%) died during follow-up; nine patients (20%) experienced progressive disease; one developed a second primary tumor (acute promyelocytic leukemia), and none developed aerodigestive second primary tumors.

Five-year progression-free survival was 80% (95% confidence interval , 65.1% - 89.1%), and overall survival was 81.3% (95% CI, 63.7% - 90.9%). These results are significantly better than the historical five-year overall survival for advanced SCCHN, which is approximately 40%.

"The bioadjuvant combination is highly effective in preventing recurrence and second primary tumors, and its role as standard therapy in advanced SCCHN is being investigated in a randomized phase 3 study," the authors write. "If these results are confirmed in phase 3 randomized trials, this therapy could benefit a large number of patients, since approximately two thirds of patients with SCCHN have developed locally advanced disease at diagnosis."

Study limitations include a relatively select group of participants who were relatively young, highly motivated, and had disease controlled up to 24 weeks from the definitive treatment.

"Nevertheless, these data suggest that the bioadjuvant therapy may offer a long-term effect in regard to prevention of recurrence, which is quite exciting, especially considering that there is no established role for adjuvant chemotherapy in high-risk SCCHN," the authors conclude. "The combination of retinoids and interferon is known to enhance radiation-induced cytotoxicity, synergistically inhibit cell growth, and promote neovascularization in SCCHN. Vitamin E was later added to our regimen because it decreases isotretinoin toxicity and also may have chemopreventive activity."

The authors report no financial conflicts of interest.

Arch Otolaryngol Head Neck Surg. 2005;131:304-307

Reviewed by Gary D. Vogin, MD

scchn, vitamin, head, isotretinoin, neck, interferon, bioadjuvant, alfa-, keelkanker, participants