Safety and Efficacy of the Long-term Adjuvant Treatment of Primary Intermediate- to High-Risk Malignant Melanoma (UICC/AJCC Stage II and III) with a Standardized Fermented European Mistletoe (Viscum album L.) Extract

PURPOSE We conducted a randomized prospective trial in selected patients with fully resected high-risk stage I and II malignant melanoma. PATIENTS AND METHODS Interferon alfa-2a (IFN-alpha 2a) 20 x 10(6) U/m2 was administered three times each week for 12 weeks by the intramuscular route. Both the treatment group (n = 131) and the control group (n = 131) were evenly balanced with regard to relevant prognostic discriminants. RESULTS The median disease-free survival (DFS) time was 2.4 years for the IFN-alpha 2a group and 2.0 years for the observation group (log-rank P = 0.19). The median survival times were 6.6 years for IFN-alpha 2a and 5.0 years for observation (log-rank P = .40). For stage I patients (n = 102), there was no apparent therapeutic advantage from IFN-alpha 2a therapy. The DFS for stage II patients was a median of 10.8 months in the control group versus 17 months in the treatment group. The overall survival time was 4.1 years for the treatment group versus 2.7 years for the control group. The differences in DFS for stage II patient were significant in a Cox model. These results must be interpreted cautiously because of subset analysis. A severe flu-like toxicity occurred in 44% of patients, 13% lost at least 10% of their baseline weight, and 45% experienced a worsening of Eastern Cooperative Oncology Group (ECOG) performance score. CONCLUSION Our findings indicate trends that suggest a possible benefit for selected patients with high-risk malignant melanoma. The results will require further study in a larger patient population for confirmation.

Download Full-text

Long-term follow-up of women enrolled in a randomized trial of adjuvant chemotherapy for early stage ovarian cancer (ICON1)

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.5509 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 5509-5509 ◽

Cited By ~ 15

Author(s):

A. C. Swart

Keyword(s):

Ovarian Cancer ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Adjuvant Treatment ◽

Early Stage ◽

Risk Groups ◽

P Value ◽

Long Term Follow Up

5509 Background: ICON1 and a meta-analysis of all relevant trials demonstrated an improvement in 5 year recurrence-free and overall survival (RFS and OS) for women with early-stage epithelial ovarian cancer (ES EOC) treated with adjuvant chemotherapy compared to no adjuvant chemotherapy. We aimed to determine if this initial benefit is maintained long-term and whether benefit is different with different risk groups of patients defined by stage, grade and histology. Method: 477 women with ES EOC were recruited from centres in Italy (271 women) UK (195) Switzerland (11) between August 1991 and January 2000. 5-year results were presented at ASCO 2001. Systematic long-term follow up was planned and completed in May 2006. Results: With a median follow-up of 9.2 years, 168 women have developed recurrent disease or died and 144 women have died. The Hazard Ratio (HR) for RFS of 0.70 in favour of adjuvant chemotherapy (95% CI 0.52–0.95 p= 0.023) translated into an improvement of 10-year absolute RFS of 10% from 57 to 67%. For OS, HR was 0.74 (95% CI 0.53–1.02 p= 0.066), a corresponding improvement in 10-year absolute OS of 8% from 64% to 72%. 26% of patients died from causes other than ovarian cancer. Stage I patients were grouped as low (Ia, grade 1), medium (Ia grade 2, Ib or Ic grade 1) and high risk (Ia, grade 3, Ib or IC grade 2 or 3, any clear cell). The test of interaction between risk groups and adjuvant treatment for RFS and OS was 0.055 and 0.13, respectively. The HR, 95%CI and p value are summarised in the table . Conclusions The long-term benefit of adjuvant treatment on RFS is confirmed. There is clear evidence that adjuvant chemotherapy reduces the risk of recurrence/death or death alone in high-risk patients but not in the low-risk group. [Table: see text] [Table: see text]

Download Full-text

AMBLor: A prognostic and stratifying biomarker for adjuvant immunotherapy of AJCC stage II melanomas.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e22094 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e22094-e22094

Author(s):

Marie Labus ◽

Robert Ellis ◽

Tom Ewen ◽

Sebastian Podlipnik ◽

Alison Greenwood ◽

...

Keyword(s):

High Risk ◽

Prognostic Biomarker ◽

Cohort Analysis ◽

Low Risk ◽

Stage Ii ◽

Patient Recruitment ◽

Assay Sensitivity ◽

Adjuvant Immunotherapy ◽

Ajcc Stage ◽

Increased Risk

e22094 Background: The success of adjuvant therapy for patients with AJCC stage III melanomas coupled with the increased risk of mortality for patients with AJCC stage IIB compared to IIIA tumours has paved the way to adjuvant immunotherapy trials for patients with sentinel lymph node (SLNB) –ve AJCC stage II disease. However, the lack of biomarkers able to appropriately stratify high-risk tumour subsets limits patient recruitment. We have recently identified the combined immunohistochemical (IHC) expression of AMBRA1 and Loricrin (AMBLor) in the epidermis overlying non-ulcerated AJCC stage I melanomas as a robust prognostic biomarker and valuable pre SLNB test. Methods: Retrospective analysis of AMBLor was performed in three geographically distinct cohorts of AJCC stage II melanomas using a clinically validated automated IHC assay and semi quantitative binary scoring analysis to define high vs low risk subgroups. Results: Data revealed loss of AMBLor overlying non-ulcerated high risk AJCC stage IIA or B tumours correlated with a significant reduction in disease free survival (DFS) at 12 years to 55% compared to 89% for patients with AMBLor low risk tumours (P = 0.015; HR 4.83, 95% CI: 2.29-10.14). Sub-cohort multivariate analysis of 80 non ulcerated stage IIB tumours also revealed reduced DFS at 12 years to 68% in AMBLor high-risk compared to 83% in AMBLor low-risk tumour subsets, with an assay sensitivity of 97% and a negative predictive value of 90%. Furthermore, sub-cohort analysis of SLNB –ve AJCC stage IIA or B tumours additionally identified 5 genuinely low risk cases in which DFS at 10 years was 100% compared to only 36% in 37 patients in which AMBLor was lost. Conclusions: Collectively these data indicate AMBLor as a novel prognostic biomarker for patients with non-ulcerated AJCC stage II melanomas as well as companion/stratifying biomarker for adjuvant immunotherapy, the use of which will increase clinician confidence for patient recruitment as well as reduce patient morbidity.

Download Full-text