Chemoimmunotherapy of advanced malignant melanoma: sequential administration of subcutaneous interleukin-2 and interferon-α after intravenous dacarbazine and carboplatin or intravenous dacarbazine, cisplatin, carmustine and tamoxifen

Atzpodien, Jens; Hänninen, Enrique Lopez; Kirchner, Hartmut; Franzke, Anke; Körfer, Alfred; Volkenandt, Matthias; Duensing, Stefan; Schomburg, A.; Chaitchik, Samario; Poliwoda, H.

doi:10.1016/0959-8049(94)00459-5

Cited by 65 publications

(20 citation statements)

References 7 publications

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“…We observed an overall objective response in 34.3% of patients treated with the combined chemoimmunotherapy which is comparable with earlier trials achieving response rates between 23% to 64% (Atkins et al, 1994;Atzpodien et al, 1995;Feun et al, 1995;Hoffmann et al, 1998;Johnston et al, 1998;Legha, 1998;Middleton et al, 2000;Pyrhonen et al, 1992;Rosenberg et al, 1999;Thompson et al, 1997). Whereas in previous clinical trials, introducing cytokines in chemotherapeutic regimens yielded an enhanced efficacy (Atkins et al, 1994;Legha et al, 1996), our results raise doubts concerning the potential benefits of the presently used dosages of IL-2 and INF-a for therapy of metastatic melanoma since objective response rates of patients treated with chemotherapy alone were similar (29.9%) to sequential chemoimmunotherapy (34.3%).…”

Section: Discussionsupporting

confidence: 90%

Combination chemotherapy with or without s.c. IL-2 and IFN-α: results of a prospectively randomized trial of the Cooperative Advanced Malignant Melanoma Chemoimmunotherapy Group (ACIMM)

et al. 2002

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The purpose of this randomized trial was to evaluate the efficacy of combination chemoimmunotherapy compared with chemotherapy alone. A total of 124 patients were randomized to receive intravenous cisplatin (35 mg m 72 , days 1 -3), carmustine (150 mg m 72 , day 1, cycles 1 and 3 only), dacarbacine (220 mg m 72 , days 1 -3) and oral tamoxifen (20 mg m 72 , daily) in combination with (n=64) or without (n=60) sequential subcutaneous IL-2 and IFN-a. In those patients who received sequential immunotherapy, each cycle of chemotherapy was followed by outpatient s.c. IL-2 (10610 6 IU m 72 , days 3 -5, week 4; 5610 6 IU m 72 , days 1, 3, 5, week 5) and s.c. IFN-a (5610 6 IU m 72 , day 1, week 4; days 1, 3, 5, week 5). The overall response rate of patients treated with the combination of chemotherapy and IL-2/IFN-a was 34.3% with seven complete responses (10.9%) and 15 partial responses (23.4%). In patients treated with chemotherapy, only, the overall response rate was 29.9% with eight complete responses (13.3%) and 10 partial responses (16.6%). There was no significant difference in median progression free survival (0 months vs 4 months) and in median overall survival (12 months vs 13 months) for combined chemoimmunotherapy and for chemotherapy, respectively.

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Section: Discussionsupporting

confidence: 90%

Combination chemotherapy with or without s.c. IL-2 and IFN-α: results of a prospectively randomized trial of the Cooperative Advanced Malignant Melanoma Chemoimmunotherapy Group (ACIMM)

et al. 2002

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“…Therefore, serum S100 might be a useful adjunct in the clinical staging and monitoring of metastatic malignant melanoma. (Atzpodien et al, 1995); treatment was continued until further disease progression occurred. Response to therapy was evaluated on an intention-totreat basis and was assessed according to WHO criteria.…”

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confidence: 99%

Elevated serum levels of S100 and survival in metastatic malignant melanoma

Buer

Probst²,

Franzke³

et al. 1997

Br J Cancer

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Summary Current reports suggest serum S100 as a prognostic marker for disease progression in advanced malignant melanoma. In this study, we assessed serum levels of S100 and multiple clinical factors in relation to overall survival in 99 patients with metastatic malignant melanoma seen at our institution between May 1990 and April 1996. For statistical analysis, we used both univariate and multivariate Cox proportional-hazards models. Elevated serum levels of S100 correlated with poor outcome in metastatic malignant melanoma (P < 0.0001), univariate analysis). Upon multivariate analysis, however, S100 added no information to known clinical prognostic parameters.

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“…10 6 U/m 2 -6 ! 10 6 U/m 2 , given at home, with two different chemotherapeutic regimens, given prior to immunotherapy [16].…”

Section: Discussionmentioning

confidence: 99%

“…The schedule of IL-2 was based on previously reported studies of Richards et al [12] and Kayat et al [14]. Although lower dosage determination was accomplished on the basis of a study done by Atpodien et al [16], in which it was reported that lower doses of IL-2, given subcutaneously at home, minimized the toxicity of the regimen and increased the compliance of the patients.…”

Section: Introductionmentioning

confidence: 99%

Subcutaneous Low Doses of Interleukin-2 and Recombinant Interferon Alpha with Carboplatin and Vinblastine in Patients with Advanced Melanoma<sup>1</sup>

Bafaloukos

Fountzilas²,

Skarlos³

et al. 1997

Oncology

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Twenty-three patients with advanced melanoma were treated with a combination of subcutaneous recombinant human interleukin-2 (IL-2), and recombinant interferon alpha-2a (IFN-α) with chemotherapy consisting of four cycles of carboplatin (300 mg/m², day 1) and vinblastine (6 mg/m², day 1), every 28 days (CV-IL-IF). IL-2 was given at a dose of 4.5 × 10⁶ U twice daily on days 3–6 and days 21–24 of each cycle; IFN-α dose was 4.5 × 10⁶ U, starting on day 2, thrice weekly. Immunotherapy was intended to continue for 6 months. Of the 23 analyzed patients, 4 (17%) achieved an objective response, including 1 complete and 3 partial responses, in nonvisceral metastatic disease. The median time to progression was 5 months and the median survival from onset of the treatment 6 months (range 1–14 months). Four patients discontinued the treatment, due to nonhaematologic toxicity; 3 for severe weakness and the 4th patient for long-lasting CNS side-effects. Other grade 3–4 toxicities included weight loss (22%), nausea and vomiting (17%) and alopecia (13%). The haematologic toxicity was acceptable. No toxic death was noted. It is con cluded that the CV-IL-IF regimen has limited activity and moderate toxicity.

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Chemoimmunotherapy of advanced malignant melanoma: sequential administration of subcutaneous interleukin-2 and interferon-α after intravenous dacarbazine and carboplatin or intravenous dacarbazine, cisplatin, carmustine and tamoxifen

Cited by 65 publications

References 7 publications

Combination chemotherapy with or without s.c. IL-2 and IFN-α: results of a prospectively randomized trial of the Cooperative Advanced Malignant Melanoma Chemoimmunotherapy Group (ACIMM)

Combination chemotherapy with or without s.c. IL-2 and IFN-α: results of a prospectively randomized trial of the Cooperative Advanced Malignant Melanoma Chemoimmunotherapy Group (ACIMM)

Elevated serum levels of S100 and survival in metastatic malignant melanoma

Subcutaneous Low Doses of Interleukin-2 and Recombinant Interferon Alpha with Carboplatin and Vinblastine in Patients with Advanced Melanoma<sup>1</sup>

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