Randomized phase II neoadjuvant study of temozolomide (TMZ) alone or with pegylated interferon-alfa 2b (PGI) in patients with resectable AJCC stage IIIC or stage IV (M1a) metastatic melanoma

8017 Background: Modifying the pharmacokinetic profile of IFN alfa-2b (PegIFN) may improve its activity and tolerability. Specifically, the conjugation of recombinant IFN alfa-2b with a 12 kDa polyethylene glycol (Peg) chain results in a prolonged half-life and has been previously demonstrated to increase efficacy in hepatitis C patients compared to nonpegylated IFNs. We therefore evaluated the combination of TMZ with PegIFN in stage IV metastatic melanoma. Methods: This open-label, phase II study was conducted by the DeCOG at 10 study sites. Eligible pts were between 18 and 75 yrs, had a histologically confirmed diagnosis of metastatic melanoma (stage IV AJCC), no brain metastases and no prior chemotherapy. Pts were required to have a Karnofsky score of > 60% as well as adequate renal, liver and bone marrow function. Informed consent from all participants and approval from the corresponding ethic committees was provided. The regimen (28 d cycles) consisted of TMZ (200 mg/m2 d 1–5) in combination with PegIFN (100 μg sc d 1, 8, 15 and 21). Patients received 2 cycles before reevaluation (WHO response criteria). OR and OS were primary and TTP and toxicity were secondary endpoints of the trial. Results: 124 pts were accrued between 10/02 and 7/04, 8 pts were ineligible or withdrew consent, and thus 116 pts were treated per protocol. At the time of data analysis, 81.0% of pts had died from melanoma and median follow up time was 9.4 months. OR was 18.1% (2 CR, 1.7%; 16 PR; 16.4%); 25.0% of pts presented with SD and 54.3 % progressed (2.6% not evaluable). Median TTP was 2.8 months, median OS 9.0 months (95% CI 7,4;10,6). Grade (gr) 3/4 leucopenia occurred in 22.8% and gr 3/4 thrombocytopenia in 20.3%. Gr 1/2 nausea and emesis experienced 37.5% of the pts; severe nausea (gr 3/4) was rare (1.7%). Liver enzyme elevation occurred in 30.5 % (26.3% gr 1/2; 4.2% gr 3). Conclusions: Combination therapy with TMZ and pegylated interferon alfa-2b constitutes a manageable treatment option in the outpatient setting for advanced metastatic melanoma. Its primary advantage is an increased patient convenience as a result of oral intake of TMZ and once weekly application of PegIFN. [Table: see text]

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A randomized phase II trial of temozolomide (TMZ) and bevacizumab (BEV) or nab-paclitaxel (nab-P)/carboplatin (CBDCA) and bevacizumab (BEV) in patients with unresectable stage IV metastatic melanoma: A North Central Cancer Treatment Group Study (N0775).

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.8532 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. 8532-8532 ◽

Cited By ~ 1

Author(s):

L. A. Kottschade ◽

V. Suman ◽

D. G. Perez ◽

R. R. McWilliams ◽

J. S. Kaur ◽

...

Keyword(s):

Treatment Group ◽

Cancer Treatment ◽

Metastatic Melanoma ◽

Phase Ii ◽

Phase Ii Trial ◽

Stage Iv ◽

North Central ◽

Randomized Phase Ii ◽

Unresectable Stage

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492 A phase II, placebo-controlled study of merimepodib (XV-497), in combination with pegylated interferon-alfa, and ribavirin in patients with chronic hepatitis C non-responsive to previous therapy with interferon-alfa and ribavirin

Journal of Hepatology ◽

10.1016/s0168-8278(04)90492-8 ◽

2004 ◽

Vol 40 ◽

pp. 145 ◽

Cited By ~ 5

Author(s):

P. Marcellin ◽

Y. Horsmans ◽

F. Nevens ◽

J.D. Grange ◽

J.P. Bronowicki ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C ◽

Chronic Hepatitis C ◽

Phase Ii ◽

Pegylated Interferon ◽

Interferon Alfa ◽

Controlled Study ◽

Previous Therapy ◽

Pegylated Interferon Alfa

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Efficacy and safety of pegylated interferon alfa-2b in moderate COVID-19: A phase II, randomized, controlled, open-label study

International Journal of Infectious Diseases ◽

10.1016/j.ijid.2021.03.015 ◽

2021 ◽

Vol 105 ◽

pp. 516-521

Author(s):

Anuja Pandit ◽

Nirav Bhalani ◽

B.L. Shashi Bhushan ◽

Parshottam Koradia ◽

Shweta Gargiya ◽

...

Keyword(s):

Phase Ii ◽

Pegylated Interferon ◽

Interferon Alfa ◽

Efficacy And Safety ◽

Open Label ◽

Open Label Study ◽

Label Study ◽

Randomized Controlled ◽

Pegylated Interferon Alfa

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Temozolomide plus pegylated interferon alfa-2b as first-line treatment for stage IV melanoma: a multicenter phase II trial of the Dermatologic Cooperative Oncology Group (DeCOG)

Annals of Oncology ◽

10.1093/annonc/mdm565 ◽

2008 ◽

Vol 19 (4) ◽

pp. 801-806 ◽

Cited By ~ 19

Author(s):

K. Spieth ◽

R. Kaufmann ◽

R. Dummer ◽

C. Garbe ◽

J.C. Becker ◽

...

Keyword(s):

Phase Ii Trial ◽

Stage Iv ◽

Pegylated Interferon ◽

Interferon Alfa ◽

Oncology Group ◽

First Line ◽

Multicenter Phase ◽

Pegylated Interferon Alfa ◽

Stage Iv Melanoma ◽

First Line Treatment

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Corrigendum to “Efficacy and safety of pegylated interferon alfa-2b in moderate COVID-19: A phase II, randomized, controlled, open-label study” [International Journal of Infectious Diseases, Volume 105, April 2021, Pages 516-521]

International Journal of Infectious Diseases ◽

10.1016/j.ijid.2021.06.030 ◽

2021 ◽

Author(s):

Anuja Pandit ◽

Nirav Bhalani ◽

B.L. Shashi Bhushan ◽

Parshottam Koradia ◽

Shweta Gargiya ◽

...

Keyword(s):

Infectious Diseases ◽

Phase Ii ◽

Pegylated Interferon ◽

Interferon Alfa ◽

Efficacy And Safety ◽

Open Label ◽

Open Label Study ◽

Label Study ◽

Randomized Controlled ◽

Pegylated Interferon Alfa

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Randomized Phase II Study of Temozolomide Given Every 8 Hours or Daily With Either Interferon Alfa-2b or Thalidomide in Metastatic Malignant Melanoma

Journal of Clinical Oncology ◽

10.1200/jco.2003.10.039 ◽

2003 ◽

Vol 21 (13) ◽

pp. 2551-2557 ◽

Cited By ~ 75

Author(s):

S. Danson ◽

P. Lorigan ◽

A. Arance ◽

A. Clamp ◽

M. Ranson ◽

...

Keyword(s):

Metastatic Melanoma ◽

Phase Ii ◽

Phase Ii Study ◽

Metastatic Malignant Melanoma ◽

Interferon Alfa ◽

Randomized Phase Ii ◽

Disease Stabilization ◽

Grade 3 ◽

Weekly Cycles ◽

To Receive

Purpose: Temozolomide is an imidazotetrazine with a mechanism of action similar to dacarbazine and equivalent activity in melanoma. It is well tolerated and is a candidate for combination chemotherapy and schedule manipulation. In this study, we combined temozolomide with interferon alfa-2b and, separately, with thalidomide, and we administered temozolomide alone in a compressed schedule. The objectives of this randomized phase II, two-center study were to determine response rates, overall survival, and tolerability of the regimens in patients with advanced metastatic melanoma. Patients and Methods: One hundred eighty-one patients with metastatic melanoma were randomly assigned to receive up to six 4-weekly cycles consisting of temozolomide 200 mg/m2 every 8 hours for five doses, or temozolomide 200 mg/m2 daily for days 1 to 5 plus interferon alfa-2b 5 MU (million International Units) subcutaneously three times a week, or temozolomide 150 mg/m2 (increased after one cycle to 200 mg/m2) daily on days 1 to 5 plus thalidomide 100 mg daily days 1 to 28. Results: The treatment arms were well balanced for known prognostic factors. Median survival was 5.3 months for 8-hourly temozolomide, 7.7 months for temozolomide/interferon, and 7.3 months for temozolomide/thalidomide; and 1-year survivals were 18%, 26%, and 24%, respectively. Response or disease stabilization occurred in 20% of patients (95% confidence interval [CI], 10% to 33%) given 8-hourly temozolomide, 21% (95% CI, 12% to 33%) given temozolomide/interferon, and 25% (95% CI, 15% to 38%) given temozolomide/thalidomide. Grade 3 or 4 nonhematologic toxicities were similar in each arm except for infection, which was more frequent with 8-hourly temozolomide. There were fewer instances of grade 3 or 4 myelotoxicity with temozolomide/thalidomide. Conclusion: Of the three regimens tested, the combination of temozolomide and thalidomide seems the most promising for future study.

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