Adjuvant treatment with vindesine in comparison to observation alone in patients with metastasized melanoma after complete metastasectomy: a randomized multicenter trial of the German Dermatologic Cooperative Oncology Group

Abstract

To evaluate the efficacy and safety of vindesine in patients with metastatic melanoma after complete metastasectomy. One hundred and forty-two patients with metastatic spread to regional sites, lymph nodes, and distant sites after complete metastasectomy were randomized to receive either treatment with vindesine for 2 years or observation alone. Vindesine 3 mg/m intravenously was administered biweekly for the first 26 weeks following 3-week intervals for an additional 26 weeks and thereafter every 4 weeks for 52 weeks. One hundred and thirty-nine patients were eligible for intent-to-treat analysis. Median follow-up time was 46 months. Median recurrence free survival was 7.9 months in the vindesine group and 7.6 months in the observational group (P=0.40). Three-year overall survival rate was 54.9% (37 patients) for patients receiving vindesine in comparison to 43.6% (31 patients) in the observation arm (P=0.07). No grade IV toxicity was observed. The two major side effects in the vindesine group were alopecia and peripheral neuropathy. Ten patients went off treatment because of grade III toxicity. Adjuvant treatment with vindesine did not significantly prolong disease free or overall survival in high-risk melanoma patients. Thus, this randomized trial did not confirm earlier reports of beneficial effects of adjuvant vindesine and can therefore not be recommended.

Malignant Melanoma S3‐Guideline “Diagnosis, Therapy and Follow‐up of Melanoma”

“…Another randomized study investigated the efficacy of vindesine versus observation in the adjuvant therapy of melanoma [357]. Unlike a prior retrospective trial [358], this analysis demonstrated no significant differences neither in recurrence-free nor in overall survival.…”

Adjuvant treatment with vindesine for metastatic melanoma: in response to the study of Eigentler et al. (2008)

“…This survival advantage, as reported by Eigentler, is short of statistical significance (P=0.07). On the strength of this P value, the authors referring to our study [2] conclude that their randomized trial did not confirm earlier reports of beneficial effect of adjuvant vindesine and therefore cannot be recommended [1].…”

“…The study of adjuvant vindesine for clinically apparent, resectable metastases from melanoma, reported by Eigentler et al [1] in the October 2008 issue of the journal, shows a discernible overall survival advantage, in favour of adjuvant vindesine versus observation. This survival advantage, as reported by Eigentler, is short of statistical significance (P=0.07).…”

Adjuvante Therapieansätze in der Onkologie: Eine kritische Nutzen-Risiko-Abwägung

“…In einer randomisierten Studie der German Dermatologic Cooperative Oncology Group, in der Hochrisiko-Patienten mit metastasiertem Melanom nach kompletter Metastasektomie mit Vindesin behandelt oder beobachtet wurden, war der Vorteil der adjuvant chemotherapeutisch behandelten Patienten weder beim krankheitsfreien Überleben (p = 0,40) noch bei der 3-Jahres-Gesamtüberlebensrate (p = 0,07) statistisch signifikant [5]. Auch zahlreiche andere randomisierte Studien zeigten keine relevanten Vorteile einer adjuvanten Chemotherapie.…”

“…Ob die Prognose durch Einsatz von pegyliertem Interferon alpha verbessert werden kann, ist derzeit noch unklar. In der Phase-III-Studie EADO, in der bei Patienten mit einer Tumordicke > 1, 5 Als obligater Standard akzeptiert ist die adjuvante Strahlentherapie zum Beispiel bei der brusterhaltenden Therapie des Mammakarzinoms. Eindeutig empfohlen wird eine Radiotherapie in der aktuellen S3-Leitlinie bei Patientinnen mit Mastektomie und > 3 befallenen axillären Lymphknoten (pN+) (Empfehlungsgrad 1); bei 1-3 befallenen Lymphknoten wird dagegen keine Empfehlung ausgesprochen (Empfehlungsgrad 0), obwohl verschiedene, allerdings ältere Studien auch in dieser Behandlungssituation einen Nutzen der adjuvanten Radiatio zeigten [14].…”