Interferon α2b and Fotemustine in Patients with Disseminated Melanoma

Kleeberg, Ulrich R.; Gawlik, Ch.; Bröcker, Eva‐B.; Boewer, Ch.; Châtelain, R; Queißer, W.; Westerhausen, M.; Rothe, B.; Friedrich, G.; Edler, Lutz

doi:10.1159/000218635

Cited by 3 publications

(1 citation statement)

References 4 publications

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“…Our response rates appear to be more favourable than were those of other studies of fotemustine monotherapy (Kleeberg et al 1995a;Falkson et al 1994), revealing an objective response in 12% and 10% respectively. In another study, combining fotemustine and IFNa2b in patients with disseminated melanoma, Kleeberg et al (1995b) reported an objective response in only 7.7% of 26 eligible patients. This appears to be lower than expected from each drug alone.…”

Section: Discussionmentioning

confidence: 99%

Fotemustine and interferon à2b in metastatic malignant melanoma

Weichenthal

Möhr

Stephan

et al. 1998

Journal of Cancer Research and Clinical Oncology

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The efficacy of treatment with fotemustine and interferon (IFN) alpha was evaluated in metastatic melanoma. A group of 50 patients with metastatic malignant melanoma were treated with a combination of IFNalpha2b and the nitrosourea fotemustine. The patients received 10 MU IFN three times weekly for 3 weeks and fotemustine at a dose of 100 mg/m2 on days 8, 15 and 22. After a 5-week rest period, patients with stabilized or responding disease received a maintenance therapy consisting of 10 MU IFN three times a week for 1 week followed by administration of fotemustine (100 mg/m2) on day 8. This cycle was repeated every 4 weeks until progression occurred. If there was complete remission (CR), treatment was stopped after an additional three cycles. Toxicity and clinical response were scored according to WHO criteria. Objective response was seen in 14 patients (28%; 95% confidence interval 15.6%-40.4%) with four CR and ten partial responses (PR). The median duration of CR was 73 weeks, that of PR 26 weeks. Toxicity was acceptable, enabling treatment on an outpatient basis. The combination of fotemustine with IFNalpha is effective and well tolerated, but there is no evident advantage over fotemustine monotherapy in the treatment of metastatic melanoma.

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Section: Discussionmentioning

confidence: 99%

Fotemustine and interferon à2b in metastatic malignant melanoma

Weichenthal

Möhr

Stephan

et al. 1998

Journal of Cancer Research and Clinical Oncology

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Sequential interferon-α2b, interleukin-2 and fotemustine for patients with metastatic melanoma

et al. 2000

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The aim of this study was the evaluation of both the antitumour activity and toxicity of an immunochemotherapeutic regimen consisting of interferon-alpha2b and interleukin-2 in combination with fotemustine for patients with metastatic melanoma. To improve the penetration of fotemustine into the brain, it was given immediately after immunotherapy, when the blood-brain barrier is still disturbed. Of the 19 patients treated, three complete remissions (CRs) and one partial remission (PR) were induced, giving an objective response rate of 21% (95% confidence interval 6-46%). The durations of the CRs were 9, 19 and 44 months; the PR lasted for 59+ months. The overall survival times for the patients with CR were 21, 25 and 70+ months, and 59+ months for the PR. For nine patients (47%, 95% confidence interval 24-71%) disease was stabilized for a median period of 8 months (range 2-18 months), resulting in a median survival of 18 months (range 10-41+ months). No haematological toxicity of World Health Organization grade 3 or more was observed and in general toxicity was low. In summary, this immunochemotherapy regimen led to long-term survival in occasional patients, and about half of the patients achieved stable disease, with prolonged treatment- and progression-free survival compared with nonresponding patients. The occurrence of brain metastases, however, was not prevented, and in fact was the site of recurrence in those patients achieving a CR. Due to its low toxicity, this protocol can be applied at a community hospital level.

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Clinical Significance of Pharmacokinetic Drug Interactions Between Interferon-?? and Antineoplastic Drugs

et al. 1999

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The major problems in chemotherapy are occasional low response rates in patients despite favourable in vitro action, the development of drug resistance and long or short term adverse effects. Therefore, in the past decade efforts have been made to circumvent these problems by combining antineoplastic drugs with biomodulating or cytoprotective agents. Most of the clinically useful drug regimens consist of a cocktail of drugs with different mechanisms of action, and hence different toxicity profiles. Dose-limiting factors in regard to toxicity and therapeutic efficacy predominate, and it is therefore clinically essential to know whether or not a pharmacokinetic drug interaction occurs. The introduction of interferon-alpha (IFNalpha) in chemotherapy is an alternative investigational approach to amplify the cytotoxicity of an antineoplastic drug in order to increase tumour response. Most of the clinical studies reported with IFNalpha provide useful information and identify major pharmacodynamic interactions, but only a few focus on and report potential pharmacokinetic interactions between antineoplastic drugs and IFNalpha in patients. The broad spectrum of antineoplastic drugs whose activity can be enhanced by IFNalpha argues for multiple levels of drug-drug interactions: protein binding (cisplatin), alteration in cellular uptake, modulation of drug target enzymes (dihydropyrimidine hydrogenase) and changes in biotransformation (tretinoin) or excretion. Pharmacokinetic and/or pharmacodynamic interactions may be beneficial (fluorouracil) or sometimes detrimental and coincidental (doxorubicin). This article focuses on observed pharmacokinetic drug interactions between IFNalpha and antineoplastic drugs and discusses possible mechanisms of action.

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Interferon α2b and Fotemustine in Patients with Disseminated Melanoma

Cited by 3 publications

References 4 publications

Fotemustine and interferon à2b in metastatic malignant melanoma

Fotemustine and interferon à2b in metastatic malignant melanoma

Sequential interferon-α2b, interleukin-2 and fotemustine for patients with metastatic melanoma

Clinical Significance of Pharmacokinetic Drug Interactions Between Interferon-?? and Antineoplastic Drugs

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