Sequential chemoimmunotherapy with cisplatin, interleukin-2, and interferon alfa-2a for metastatic melanoma.

Khayat, David; Borel, Christian; Tourani, Jean-Marc; Benhammouda, A.; Antoine, E.; Rixe, Olivier; Vuillemin, E.; Bazex, P. A.; Thill, L.; Franks, Ruth

doi:10.1200/jco.1993.11.11.2173

Cited by 134 publications

(37 citation statements)

References 18 publications

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“…We observed that biochemotherapy (combination of IL-2, interferon, and CVD chemotherapy regimen) is associated with better response rates and survival duration than other multi-drug regimens (Richards et al, 1992;Khayat et al, 1993;Atkins et al, 1994;Legha et al, 1996Legha et al, , 1998Thompson et al, 1997;Johnston et al, 1998;O'Day et al, 1999;Flaherty et al, 2001;Hauschild et al, 2001;Atzpodien et al, 2002;Keilholz et al, 202 BEDIKIAN ET AL. 2005). However, the prospectively-randomized Phase III trials failed to firmly establish the superiority of IL-2-based regimens over chemotherapy Hauschild et al, 2001;Atzpodien et al, 2002;Eton et al, 2002;Atkins et al, 2003).…”

Section: Introductionmentioning

confidence: 90%

“…The contribution of biotherapy including IL-2 to the efficacy of biochemotherapy has been evaluated in several Phase III trials. These trials varied in sample size, choice of chemotherapy regimen, dose schedule of IL-2, and choice of control arm (Khayat et al, 1993;Johnston et al, 1998;Rosenberg et al, 1999;Hauschild et al, 2001;Atzpodien et al, 2002;Eton et al, 2002;Atkins et al, 2003;Keilholz et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

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Systemic Therapy for Unresectable Metastatic Melanoma: Impact of Biochemotherapy on Long-Term Survival

Bedikian

Johnson

Warneke

et al. 2008

Journal of Immunotoxicology

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The impact of systemic therapy on survival of patients with metastatic melanoma is uncertain. This retrospective analysis aimed to compare the response rates and survival of patients without prior therapy with cisplatin, vinblastine, dacarbazine and interleukin (IL)-2 who were treated with biochemotherapy (containing these drugs plus interferon-α) with those of patients who received combination chemotherapy with and without interferon-α (chemotherapy ± IFN). Records for 616 chemo-naïve patients with unresectable metastatic melanoma who were treated on eight Phase II/III clinical trials between 1987 and 2001 were combined and reviewed The database included patients with melanoma of the skin (497 cases), unknown primary melanoma (83 cases), mucosal melanoma (21 cases), and uveal melanoma (15 cases). Two hundred sixty-four patients received biochemotherapy, and 352 received chemotherapy ± IFN. The overall response rate (complete and partial) of patients treated with biochemotherapy was 52% (138/264) compared with 35% (122/352) among patients treated with chemotherapy ± IFN regimens. The median survival times for patients in the biochemotherapy and chemotherapy ± IFN groups were 12.2 mo (95% CI: 10.9, 13.5) and 9.1 mo (95% CI: 8.1, 10.4), respectively ( p < 0.0001). Five-year overall survival rates of patients treated with biochemotherapy and chemotherapy ± IFN were 17% and 7% ( p = 0.0004), respectively. Ten-year overall survival rates were 15% and 5% ( p = 0.0001), respectively. We conclude from these studies that patients benefited more from biochemotherapy than other regimens.

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Section: Introductionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Systemic Therapy for Unresectable Metastatic Melanoma: Impact of Biochemotherapy on Long-Term Survival

Bedikian

Johnson

Warneke

et al. 2008

Journal of Immunotoxicology

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“…Recently, a combination of chemo-and immunotherapy has been investigated in several phase II studies (Khayat et al, 1993;Legha et al, 1998;O'Day et al, 1999;Richards et al, 1999) with responses of 40 -60%. However, in a recent phase III trial, survival did not improve with the addition of high-dose IL2 and IFNa to chemotherapy compared to chemotherapy alone (Rosenberg et al, 1999).…”

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confidence: 99%

Temozolomide followed by combined immunotherapy with GM-CSF, low-dose IL2 and IFNα in patients with metastatic melanoma

et al. 2003

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The purpose of this study is to determine the toxicity and efficacy of temozolomide (TMZ) p.o. followed by subcutaneous (s.c.) lowdose interleukin-2 (IL2), granulocyte -monocyte colony stimulating factor (GM-CSF) and interferon-a 2b (IFNa) in patients with metastatic melanoma. A total of 74 evaluable patients received, in four separate cohorts, escalating doses of TMZ (150 -250 mg m À2 ) for 5 days followed by s.c. IL2 (4 MIU m À2 ), GM-CSF (2.5 mg kg À1 ) and IFNa (5 MIU flat) for 12 days. A second identical treatment was scheduled on day 22 and cycles were repeated in stable or responding patients following evaluation. Data were analysed after a median follow-up of 20 months (12 -30 months). The overall objective response rate was 31% (23 out of 74; confidence limits 20.8 -42.9%) with 5% CR. Responses occurred in all disease sites including the central nervous system (CNS). Of the 36 patients with responding or stable disease, none developed CNS metastasis as the first or concurrent site of progressive disease. Median survival was 252 days (8.3 months), 1 year survival 41%. Thrombocytopenia was the primary toxicity of TMZ and was dose-and patientdependent. Lymphocytopenia (grade 3 -4 CTC) occurred in 48.5% (34 out of 70) fully monitored patients following TMZ and was present after immunotherapy in two patients. The main toxicity of combined immunotherapy was the flu-like syndrome (grade 3) and transient liver function disturbances (grade 2 in 20, grade 3 in 15 patients). TMZ p.o. followed by s.c. combined immunotherapy demonstrates efficacy in patients with stage IV melanoma and is associated with toxicity that is manageable on an outpatient basis.

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“…To date, the combination of immunotherapy (IFN-a and/or IL-2) with multidrug chemotherapy (mostly including DTIC and cisplatin) has yielded the highest response rates in metastatic melanoma, with response rates up to 70% Richards et al, 1992;Khayat et al, 1993;Atkins et al, 1994;Buzaid and Legha, 1994). However, all these results were obtained in (mostly single centre) phase II studies.…”

Section: Discussionmentioning

confidence: 99%

“…Phase II results of DTIC plus IL-2 did not suggest a clear benefit for this combination (Stoter et al, 1991;Fiedler et al, 1992). High response rates of 42-73% have been achieved in (mostly single centre) phase II studies with combinations of IL-2, IFN-ax and cisplatin (Khayat et al, 1993), IL-2, IFNax and CVD (Buzaid and Legha, 1994), IL-2, cisplatin, DTIC and tamoxifen (Atkins et al, 1994), and IL-2, IFN-ax, cisplatin, carmustine, DTIC and tamoxifen (Richards et al, 1992). The median duration of response and survival in these studies was reported to be up to 9 months and 14 months respectively.…”

mentioning

confidence: 99%

Chemoimmunotherapy with bleomycin, vincristine, lomustine, dacarbazine (BOLD) plus interferon α for metastatic melanoma: a multicentre phase II study

Punt

Herpen²,

Jansen³

et al. 1997

Br J Cancer

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Summary High response rates in patients with metastatic melanoma have been achieved with combination chemoimmunotherapy. A response rate of 62% in 45 patients has been reported for treatment with dacarbazine, bleomycin, vincristine, lomustine (BOLD) plus interferon ax (IFN-ax). We conducted a multicentre phase 11 study to confirm these results. Melanoma patients with distant metastases were treated as outpatients with dacarbazine 200 mg m-2 on days 1-5, vincristine 1 mg m-2 on days 1 and 4, bleomycin 15 mg on days 2 and 5 i.v. and lomustine 80 mg orally on day 1, repeated every 4 weeks. IFN-a-2b was initiated s.c. on day 8 at 3 MU daily for 6 weeks, and 6 MU t.i.w. thereafter. Forty-three patients entered the study. The median number of metastatic sites was three (range 1-5), and 81% of patients had visceral metastases. Nine patients had brain metastases, and seven patients were systemically pretreated. Among the 41 patients that were evaluable for response, the response rate was 27% (95% Cl 14-43%), with one complete and ten partial remissions. The response rate in 25 previously untreated patients without brain metastases was 40% (95% Cl 21-61%). Median duration of response was 6 (range 2-14+) months; median overall survival was 5 (1-26) months. The main toxicity was malaise/fatigue. We confirm that BOLD plus IFN-aX has activity in metastatic melanoma. The lower response rate in our study compared with the previous report is probably related to patient selection, as in the previous study 46% of patients had stage IlIl disease, whereas all our patients had stage IV disease, which is associated with a worse prognosis.

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Sequential chemoimmunotherapy with cisplatin, interleukin-2, and interferon alfa-2a for metastatic melanoma.

Abstract: These results seem to indicate a possible synergy between CDDP/rIL-2 and IFN alpha in MM.

Cited by 134 publications

References 18 publications

Systemic Therapy for Unresectable Metastatic Melanoma: Impact of Biochemotherapy on Long-Term Survival

Systemic Therapy for Unresectable Metastatic Melanoma: Impact of Biochemotherapy on Long-Term Survival

Temozolomide followed by combined immunotherapy with GM-CSF, low-dose IL2 and IFNα in patients with metastatic melanoma

Chemoimmunotherapy with bleomycin, vincristine, lomustine, dacarbazine (BOLD) plus interferon α for metastatic melanoma: a multicentre phase II study

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