Central nervous system failure in melanoma patients: results of a randomised, multicentre phase 3 study of temozolomide- and dacarbazine- based regimens

Chiarion-Sileni, Vanna; Guida, Michele; Ridolfi, Laura; Romanini, Antonella; Bianco, Paola Del; Pigozzo, Jacopo; Brugnara, S.; Colucci, Giuseppe; Ridolfi, Ruggero; Salvo, Gian Luca De

doi:10.1038/bjc.2011.178

Cited by 53 publications

(40 citation statements)

References 23 publications

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“…Die Kombination Fotemustin plus WBRT verzögerte im Vergleich zu Fotemustin allein in einer Phase-III-Studie mit 76 Melanompatienten mit Hirnmetastasen zwar signifikant die zerebrale Progression, allerdings ohne dass die Kombination einen signifikanten Einfluss auf das objektive Ansprechen und das Gesamtüberleben hatte [17]. Das Auftreten von Hirnfiliae scheint sich bei Melanompatienten durch liquorgängige Medikamente zu verzögern: Fotemustin und Temozolomid (jeweils vs. Dacarbazin) verlängerten die Zeit bis zur Hirnmetastasierung [18,19]. …”

Section: Paradigmenwechsel In Der Therapie Von Hirnmetastasen Beim Meunclassified

ZNS-Metastasen - eine interdisziplinäre Herausforderung

Steinbach¹,

Vordermark

Gutzmer

2013

Oncol Res Treat

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Section: Paradigmenwechsel In Der Therapie Von Hirnmetastasen Beim Meunclassified

ZNS-Metastasen - eine interdisziplinäre Herausforderung

Steinbach¹,

Vordermark

Gutzmer

2013

Oncol Res Treat

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“…Chiarion-Sileni et al . [22], in a phase III randomized study, showed the inefficacy of temozolomide in preventing CNS metastasis from melanoma, although they suggested that temozolomide may delay the onset of CNS disease. In the present study, the median time to CNS involvement was only 5.33 months, which undermines that claim.…”

Section: Discussionmentioning

confidence: 99%

Phase I trial of biochemotherapy with cisplatin, temozolomide, and dose escalation of nab-paclitaxel combined with interleukin-2 and interferon-α in patients with metastatic melanoma

et al. 2014

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The primary objective of this study was to determine the safety, toxicity, and maximum tolerated dose of nanoparticle albumin-bound (nab)-paclitaxel as part of biochemotherapy for metastatic melanoma and to determine whether substituting nab-paclitaxel for less potent agents could increase response rates and duration. Treatment consisted of intravenous cisplatin (20 mg/m2) on days 1–4, oral temozolomide (250 mg/m2) on days 1–3, subcutaneous interferon-α (5 × 106 IU/m2) on days 1–5, and continuous intravenous interleukin-2 (9 × 106 IU/m2) for 96 h on days 1–4. A standard 3 + 3 dose escalation method was used; the nab-paclitaxel starting dose was 100 mg/m2 on day 1 and 70 mg/m2 on day 5. The treatment cycle was repeated every 3 weeks and toxicity was assessed weekly. Ten patients were enrolled. Dose-limiting toxicities included diarrhea, transaminasemia, and neutropenia. The maximum tolerated dose was not identified because the nab-paclitaxel dose on day 1 at the lowest planned dose (80 mg/m2) caused dose-limiting toxicity in two of five patients. Of the nine patients who were evaluable for response, five had a partial response. The median time to disease progression was 5.30 months and the median overall survival was 8.73 months. Six patients developed central nervous system metastasis at a median of 5.33 months after treatment initiation. Biochemotherapy including nab-paclitaxel according to the doses and schedule regimen used in the present study has significant toxicity. Substituting dacarbazine with temozolomide did not prevent central nervous system metastasis in patients with metastatic melanoma.

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“…Effect of temozolomide in comparison with dacarbazine in the treatment of patients with advanced metastatic malignant melanoma Complete response: The summary of RR for complete response of temozolomide in comparison with dacarbazine in patients with advanced metastatic malignant melanoma for three included trials [11][12][13] was 0.83 (95% CI = 0.26-2.64), which was nonsignificant (P = 0.76; Fig. 2a).…”

Section: Efficacymentioning

confidence: 96%

Efficacy and side effects of dacarbazine in comparison with temozolomide in the treatment of malignant melanoma

Teimouri¹,

Nikfar²,

Abdollahi³

2013

Melanoma Research

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The widespread prevalence of melanoma, one of the most malignant forms of skin cancer, is increasing rapidly. Two chemotherapeutic regimens are commonly used for the palliative treatment of malignant melanoma: intravenous administration of single-agent dacarbazine or oral administration of temozolomide. The aim of this study was to compare the effectiveness and side effects of dacarbazine with those of temozolomide through a meta-analysis. A thorough literature bibliography search was conducted up to 2012 to gather and review all randomized clinical trials comparing the use of dacarbazine with that of temozolomide in the treatment of malignant melanoma. Three head-to-head randomized clinical trials comprising 1314 patients met the criteria and were included. Comparison of temozolomide with dacarbazine yielded a nonsignificant relative risk (RR) of 0.83 [95% confidence interval (CI) = 0.26-2.64, P = 0.76] for complete response, a nonsignificant RR of 1.05 (95% CI = 0.85-1.3, P = 0.65) for stable disease, and a nonsignificant RR of 2.64 (95% CI = 0.97-1.36, P = 0.11) for disease control rate. The RR for nonhematologic side effects and hematologic side effects, such as anemia, neutropenia, and thrombocytopenia, of temozolomide compared with dacarbazine in patients with malignant melanoma was nonsignificant in all cases, but the RR for lymphopenia of temozolomide compared with dacarbazine was 3.79 (95% CI = 1.38-10.39, P = 0.01), which was significant. Although it is easier to administer oral medication, according to the results, there is no significant difference in the efficacy and side effects of these two drugs. Owing to the higher cost of treatment with temozolomide and the increased prevalence of lymphopenia on using temozolomide, use of dacarbazine as the first choice treatment for malignant melanoma is suggested.

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Central nervous system failure in melanoma patients: results of a randomised, multicentre phase 3 study of temozolomide- and dacarbazine- based regimens

Cited by 53 publications

References 23 publications

ZNS-Metastasen - eine interdisziplinäre Herausforderung

ZNS-Metastasen - eine interdisziplinäre Herausforderung

Phase I trial of biochemotherapy with cisplatin, temozolomide, and dose escalation of nab-paclitaxel combined with interleukin-2 and interferon-α in patients with metastatic melanoma

Efficacy and side effects of dacarbazine in comparison with temozolomide in the treatment of malignant melanoma

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