Prolonged Survival of Patients Receiving Active Immunotherapy With Canvaxin Therapeutic Polyvalent Vaccine After Complete Resection of Melanoma Metastatic to Regional Lymph Nodes

Abstract

ObjectiveTo determine whether adjuvant postoperative active specific immunotherapy with a therapeutic polyvalent vaccine (PV) called Canvaxin can prolong survival following complete resection of melanoma metastatic to regional nodes (American Joint Committee on Cancer [AJCC] stage III melanoma). Summary Background DataDespite complete lymphadenectomy, 5-year overall survival (OS) for patients with melanoma metastatic to regional lymph nodes is only 20% to 50%, depending on the number of tumor-involved nodes. In 1984, the authors began phase II trials of Canvaxin PV as postsurgical adjuvant therapy for AJCC stage III melanoma. MethodsPatients who received PV between 1984 and 1998 were compared with patients who did not receive PV postsurgical therapy between 1971 and 1998. The seven covariates recently defined by the AJCC Melanoma Staging Committee (number of metastatic nodes, palpable status, ulceration, age, primary site, pT stage, and gender) were included by Cox regression in a multivariate model of OS. A computerized program matched PV and non-PV patients by these covariates. ResultsOf 2,602 patients who underwent complete lymphadenectomy for AJCC stage III melanoma with regional nodal metastases and were followed up by the same team of oncologists between 1971 and 1998, 935 received PV and 1,667 did not.Median OS and 5-year OS were significantly higher in PV than non-PV patients (56.4 vs. 31.9 months and 49% vs. 37%, respectively; P ϭ .0001). When the non-PV patients were matched by the four most significant covariates, 447 matched pairs were formed between patients seen before or after January 1, 1985, and the OS was not different between the two time periods (P ϭ .789). However, when the PV patients were matched with non-PV patients by six covariates forming 739 pairs, the PV patients survived longer (P ϭ .0001). Detailed analysis of the 1,505 patients who were seen or who began vaccine therapy within 4 months after lymphadenectomy, and who had more complete data on the seven prognostic covariates showed that median OS and 5-year OS were higher in 445 PV patients than in 1,060 non-PV patients: 70.4 versus 31 months and 52% versus 37%, respectively (P ϭ .0001). Multivariate Cox regression analysis identified six significant prognostic factors: number of metastatic nodes, size of metastatic nodes, pT stage, ulceration, age, and PV therapy. PV therapy reduced the relative risk of death to 0.64 (95% confidence interval, 0.55-0.76) (P ϭ .0001); sex and site of primary were of borderline significance. ConclusionsThis large single-institution study independently confirmed the significance of prognostic covariates in the new AJCC staging system. By using modern statistical methods that controlled for all known prognostic factors, it also demonstrated PV's ability to significantly enhance OS. A multicenter phase III randomized trial is underway to validate the efficacy of PV as a postsurgical adjuvant.

Endogenous immune response to gangliosides in patients with confined prostate cancer

“…Because it is not possible to detect the quantity of specific tumor gangliosides shed into the circulation, we used a sensitive ELISA protocol for antiganglioside IgM; this assay has been validated for screening sera of melanoma patients receiving a cancer vaccine in a Phase III multicenter clinical trial based at the John Wayne Cancer Institute. 47 In our study, this ELISA revealed that serum levels of anti-GD1a IgM antibody were significantly higher in patients with organ-confined CaP than in healthy controls (p 5 0.02), patients with BPH (p < 0.008) or patients with unconfined CaP (p 5 0.002). The uniquely elevated endogenous immune response to GD1a in our study merits further investigation as an immunologic marker of neoplastic transformation of prostate epithelial cells.…”

“…GD2 is considered to be immunogenic in human cancers 41,44 and considered as a potential target for both passive [44][45][46] and active specific immunotherapies 47 of melanoma. Although we could not observe any significant difference in the anti-GD2 response among our study groups, we did not test the sera against O-acetylated GD2 only.…”

Favorable overall survival in stage III melanoma patients after adjuvant dendritic cell vaccination

“…Still, our controls had a similar 5-year survival rate as a comparable group of melanoma patients after RLND reported in recent literature. 33 A randomized clinical trial with DC vaccination in the adjuvant setting is needed to prospectively validate the efficacy of DC-vaccines in the adjuvant treatment following RLND for melanoma. The introduction of adjuvant DC vaccination after RLND would not interfere with the current standard of care, especially in Europe where IFN-a is not recommended.…”

Incidence of BRAF Oncogene Mutation and Clinical Relevance for Primary Cutaneous Melanomas

“…The lack of correlation between BRAF mutation and Breslow thickness could be suggestive of the unrelatedness of BRAF mutation to genetic instability during early stages of primary tumor growth. Breslow thickness is known as one of the strongest prognostic factors in early stage melanoma (14,19). BRAF mutation acquisition is unlikely attributable to primary tumor growth.…”

“…Proportional hazards test was used to isolate factors influencing the survival. Multivariate analyses considered age, sex, Breslow thickness, presence or absence of lymph node metastasis, site, and presence or absence of BRAF mutation (14). All statistical calculations were performed with SAS software version 3.2.1 (SAS Institute, Cary, NC).…”