Clinical and histologic involvement of regional lymph nodes in malignant melanoma. Adjuvant vindesine improves survival

Abstract

Background. This report is a study of prognostic factors, including adjuvant chemotherapy, that influence survival of patients with malignant melanoma who have clinical and pathologic involvement of regional lymph nodes. Methods. A total of 169 evaluable patients with malignant melanoma metastatic to regional lymph nodes were registered consecutively and prospectively between June 1977 and December 1986 in the computerized data base of the melanoma registry at Westminster Hospital. Eighty‐seven of these patients received adjuvant chemotherapy with vindesine after resection of palpable metastatic lymph nodes, and 82 had no systemic treatment after surgery. All were followed up for at least 2 years (median, 8 years) after involvement of regional lymph nodes was noted or until death. Statistical analyses included simple life‐table comparisons, unadjusted for covariates. In addition, Breslow's thickness, ulceration of the primary lesion, its anatomical location, number of regional lymph nodes histologically involved, dissection site, patient age and sex, and adjuvant vindesine therapy were included as covariates in Cox regression models. Results. The disease‐free interval (P = 0.0001), time to dissemination from lymph node metastases (P < 0.0001), survival time after lymph node dissection (P = 0.0227) and overall survival time after initial diagnosis of malignant melanoma (P = 0.0095, log‐rank chi‐square test) were superior for the 87 patients who received adjuvant chemotherapy with vindesine. Cox regression analysis confirmed adjuvant vindesine as a highly significant variable influencing all of these outcomes, including overall survival time after first diagnosis (P = 0.003). Conclusions. The apparent effect of adjuvant vindesine on overall survival in this study is large (hazard ratio, 0.52) and highly statistically significant. Adjuvant vindesine therapy merits consideration for malignant melanoma metastatic to regional lymph nodes. However, these results observed in concurrent, but nonrandomized, patients clearly require confirmation.

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

“…Unlike a prior retrospective trial [358], this analysis demonstrated no significant differences neither in recurrence-free nor in overall survival. Thus, no adjuvant chemotherapy has until now been proven to be beneficial.…”

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

“…Sample size calculation was performed according to published data by Retsas et al [12] assuming a 3-year survival rate of 25% for patients in the observation group and 40% in the treatment group. Sixty-three patients were required in each group to achieve 80% power to detect this 25% increase in overall survival after 4 years, assuming a P-value of 0.05.…”

“…Back in 1994, Retsas and colleagues [12] reported about a significant benefit in 5-year overall survival after complete lymph node dissection in patients treated with vindesine. This trial, however, did not have a randomized design and the analysis was based on historical control patients.…”

Langzeitergebnisse der adjuvanten Chemotherapie nach therapeutischer Lymphknotendissektion beim malignen Melanom der Haut

“…Im Jahre 1994 wurde von Retsas et al eine nicht randomisierte Studie zur adjuvanten Therapie nach tastbaren Lymphknotenmetastasen publiziert, wobei das Vinca-Alkaloid Vindesine über 2 Jahre zur Anwendung kam [30]. Die 5-Jahres-Überlebensrate von 87 Patienten mit adjuvanter Vindesine-Therapie war mit 49% signifikant besser als die Überlebensrate von 28% für die 82 Patienten der Kontrollgruppe.…”

“…30% dieser Subpopulation nach einem Intervall von bis zu 20 Jahren tastbare Lymphknotenmetastasen, wobei 2/3 der Absiedlungen in den ersten 2 Jahren nach der Exzision des Primärtumors diagnostiziert werden [7,27,32]. Aufgrund des späteren Diagnosezeitpunktes ("lead time bias"; [28]), möglicherweise auch aufgrund der jetzt deutlich höheren Tumorlast in den Lymphknoten ist die Prognose in der Patientengruppe mit tastbaren Lymphknotenmetastasen offenbar deutlich schlechter (5-Jahres-Überlebens-raten 13%-36%; [17,25,27,29,30,33] …”