A randomized phase II trial of 1 month versus 1 year of adjuvant high-dose interferon alfa-2b in high-risk acral melanoma patients.

PURPOSE: High-dose interferon alfa-2b (IFNα2b) is the only established adjuvant therapy of resectable high-risk melanoma. GM2-KLH/QS-21 (GMK) is a chemically defined vaccine that is one of the best developed of a range of vaccine candidates for melanoma. A single-institution phase III trial conducted at Memorial Hospital served as the impetus for an intergroup adjuvant E1694/S9512/C509801 trial, which recently completed enrollment of 880 patients. To build on the apparent benefit of IFNα2b in resectable high-risk American Joint Committee on Cancer (AJCC) stage IIB or III melanoma, this phase II study was designed to evaluate the combination of GMK and IFNα2b. The E2696 trial was undertaken to evaluate the toxicity and other effects of the established adjuvant high-dose IFNα2b regimen in relation to immune responses to GMK and to evaluate the potential clinical and immunologic effects of the combined therapies. PATIENTS AND METHODS: This trial enrolled 107 patients with resectable high- or very high–risk melanoma (AJCC stages IIB, III, and IV). RESULTS: The results demonstrate that IFNα2b does not significantly inhibit immunoglobulin M or G serologic responses to the vaccine and that the combination of high-dose IFNα2b and GMK is well tolerated in this patient population. CONCLUSION: Cox analysis of the results of the combination with IFNα2b show improvement in the relapse-free survival of patients with very high–risk melanoma (including those with resectable M1 disease).

Download Full-text

Systemic Immune-Inflammation Index and Circulating T-Cell Immune Index Predict Outcomes in High-Risk Acral Melanoma Patients Treated with High-Dose Interferon

Translational Oncology ◽

10.1016/j.tranon.2017.06.004 ◽

2017 ◽

Vol 10 (5) ◽

pp. 719-725 ◽

Cited By ~ 9

Author(s):

Jiayi Yu ◽

Xiaowen Wu ◽

Huan Yu ◽

Siming Li ◽

LiLi Mao ◽

...

Keyword(s):

T Cell ◽

High Risk ◽

High Dose ◽

Acral Melanoma ◽

Melanoma Patients ◽

Immune Inflammation ◽

High Dose Interferon

Download Full-text

Phase II trial of combination biotherapy of high-dose interferon alfa-2b and tremelimumab for recurrent inoperable stage III or stage IV melanoma

Journal of Clinical Oncology ◽

10.1200/jco.2008.26.15_suppl.9009 ◽

2008 ◽

Vol 26 (15_suppl) ◽

pp. 9009-9009 ◽

Cited By ~ 6

Author(s):

A. A. Tarhini ◽

S. S. Moschos ◽

J. J. Schlesselman ◽

J. Shope-Spotloe ◽

M. Demark ◽

...

Keyword(s):

Phase Ii ◽

Phase Ii Trial ◽

Stage Iv ◽

Interferon Alfa ◽

Stage Iii ◽

High Dose ◽

High Dose Interferon ◽

Stage Iv Melanoma

Download Full-text

Association of immune-inflammation index with outcome of high-risk acral melanoma patients treated with adjuvant high-dose interferon.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.15_suppl.e21070 ◽

2016 ◽

Vol 34 (15_suppl) ◽

pp. e21070-e21070 ◽

Cited By ~ 3

Author(s):

Jiayi Yu ◽

Si Ming Li ◽

Yan Kong ◽

Lu Si ◽

Xinan Sheng ◽

...

Keyword(s):

High Risk ◽

High Dose ◽

Acral Melanoma ◽

Melanoma Patients ◽

Immune Inflammation ◽

High Dose Interferon

Download Full-text

Randomized phase II trial of high-dose interleukin-2 either alone or in combination with interferon alfa-2b in advanced renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.1993.11.4.661 ◽

1993 ◽

Vol 11 (4) ◽

pp. 661-670 ◽

Cited By ~ 135

Author(s):

M B Atkins ◽

J Sparano ◽

R I Fisher ◽

G R Weiss ◽

K A Margolin ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Phase Ii ◽

Renal Cell ◽

Phase Ii Trial ◽

Interleukin 2 ◽

Interferon Alfa ◽

High Dose ◽

Randomized Phase Ii ◽

To Receive

PURPOSE To determine better the activity of high-dose interleukin-2 (IL-2) either alone or in combination with interferon alfa-2b (IFN; Schering-Plough, Kenilworth, NJ) in patients with metastatic renal cell carcinoma, the IL-2 Working Group initiated a randomized phase II trial. PATIENTS AND METHODS Patients were randomly assigned to receive treatment with either IL-2 (Chiron Corp, Emeryville, CA) 1.33 mg/m2 (approximately 600,000 IU/kg) alone or IL-2 0.8 mg/m2 and IFN 3 x 10(6) U/m2 administered by bolus intravenous injection every 8 hours, days 1 to 5 and 15 to 19 (maximum, 28 doses). All patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and normal organ function. After 28 patients were entered onto each arm, the IL-2/IFN arm was closed because of a failure to meet predetermined efficacy criteria. An additional 43 patients (total, 71) were assigned to receive IL-2 alone. RESULTS Toxicities were similar for both study arms. Hypotension requiring pressors was the most frequent dose-limiting toxicity. Only 11 of 99 patients experienced severe toxicity; there were no irreversible side effects or treatment-related deaths. Responses were seen in three of 28 patients (11%) on IL-2/IFN (three partial responses [PRs] lasting 14, 7, and 7 months) and 12 of 71 patients (17%) on IL-2 alone (four complete responses [CRs] and eight PRs). Six of the partial responders on IL-2 and two on IL-2/IFN experienced greater than 90% reduction in tumor mass. Ten of the 12 responders to IL-2 have ongoing responses of 12+ to 26+ months in duration. CONCLUSION We conclude that both IL-2 and IL-2/IFN therapy have activity in metastatic renal cell carcinoma. In particular, therapy with high-dose IL-2 alone produces meaningful and durable responses with manageable and reversible toxicity. This study supports the contention that high-dose IL-2 represents the treatment of choice in selected patients with advanced renal cell carcinoma.

Download Full-text

Dose-Dependent Treatment Benefit in High-Risk Melanoma Patients Receiving Adjuvant High-Dose Interferon Alfa-2b

Cancer Biotherapy & Radiopharmaceuticals ◽

10.1089/cbr.2005.20.280 ◽

2005 ◽

Vol 20 (3) ◽

pp. 280-289 ◽

Cited By ~ 8

Author(s):

Michael Fluck ◽

Darab Kamanabrou ◽

Andrea Lippold ◽

Martina Reitz ◽

Jens Atzpodien

Keyword(s):

High Risk ◽

Interferon Alfa ◽

High Dose ◽

Treatment Benefit ◽

High Risk Melanoma ◽

Risk Melanoma ◽

Melanoma Patients ◽

Dose Dependent ◽

High Dose Interferon

Download Full-text

High-Dose Interferon Alfa-2b Significantly Prolongs Relapse-Free and Overall Survival Compared With the GM2-KLH/QS-21 Vaccine in Patients With Resected Stage IIB-III Melanoma: Results of Intergroup Trial E1694/S9512/C509801

Journal of Clinical Oncology ◽

10.1200/jco.2001.19.9.2370 ◽

2001 ◽

Vol 19 (9) ◽

pp. 2370-2380 ◽

Cited By ~ 676

Author(s):

John M. Kirkwood ◽

Joseph G. Ibrahim ◽

Jeffrey A. Sosman ◽

Vernon K. Sondak ◽

Sanjiv S. Agarwala ◽

...

Keyword(s):

Overall Survival ◽

High Risk ◽

Interferon Alfa ◽

High Dose ◽

Treatment Benefit ◽

Significant Treatment ◽

Melanoma Patients ◽

Intergroup Trial ◽

Resected Stage ◽

High Dose Interferon

PURPOSE: Vaccine alternatives to high-dose interferon alfa-2b therapy (HDI), the current standard adjuvant therapy for high-risk melanoma, are of interest because of toxicity associated with HDI. The GM2 ganglioside is a well-defined melanoma antigen, and anti-GM2 antibodies have been associated with improved prognosis. We conducted a prospective, randomized, intergroup trial to evaluate the efficacy of HDI for 1 year versus vaccination with GM2 conjugated to keyhole limpet hemocyanin and administered with QS-21 (GMK) for 96 weeks (weekly × 4 then every 12 weeks × 8). PATIENTS AND METHODS: Eligible patients had resected stage IIB/III melanoma. Patients were stratified by sex and number of positive nodes. Primary end points were relapse-free survival (RFS) and overall survival (OS). RESULTS: Eight hundred eighty patients were randomized (440 per treatment group); 774 patients were eligible for efficacy analysis. The trial was closed after interim analysis indicated inferiority of GMK compared with HDI. For eligible patients, HDI provided a statistically significant RFS benefit (hazard ratio [HR] = 1.47, P = .0015) and OS benefit (HR = 1.52, P = .009) for GMK versus HDI. Similar benefit was observed in the intent-to-treat analysis (RFS HR = 1.49; OS HR = 1.38). HDI was associated with a treatment benefit in all subsets of patients with zero to ≥ four positive nodes, but the greatest benefit was observed in the node-negative subset (RFS HR = 2.07; OS HR = 2.71 [eligible population]). Antibody responses to GM2 (ie, titers ≥ 1:80) at days 29, 85, 365, and 720 were associated with a trend toward improved RFS and OS (P2 = .068 at day 29). CONCLUSION: This trial demonstrated a significant treatment benefit of HDI versus GMK in terms of RFS and OS in melanoma patients at high risk of recurrence.

Download Full-text