Cytokines in Metastatic Renal Cell Carcinoma: Is It Useful to Switch to Interleukin-2 or Interferon After Failure of a First Treatment?

Escudier, Bernard; Chevreau, Christine; Lasset, Christine; Douillard, Jean Yves; Ravaud, Alain; Fabbro, Michel; Caty, Armelle; Rossi, Jean François; Viens, Patrice; Bergerat, J. P.; Savary, J.; Négrier, Sylvie

doi:10.1200/jco.1999.17.7.2039

Cited by 85 publications

(39 citation statements)

References 12 publications

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“…Of those patients, eight showed PD at study entry, of which two patients (6,23) with previously progressive liver lesions and others after progression under previous immunotherapy regimens. These are events that rarely occur, even after 'standard' cytokine treatment (Lissoni et al, 1994;Escudier et al, 1999;Motzer et al, 2002). Collectively, these results suggest that WX-G250 has the capacity of modulating the natural history of metastasised RCC with a safe toxicity profile.…”

Section: Discussionmentioning

confidence: 84%

A phase II trial of chimeric monoclonal antibody G250 for advanced renal cell carcinoma patients

Bleumer¹,

Knuth²,

Oosterwijk³

et al. 2004

Br J Cancer

158

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Chimeric monoclonal antibody G250 (WX-G250) binds to a cell surface antigen found on 490% of renal cell carcinoma (RCC). A multicentre phase II study was performed to evaluate the safety and efficacy of WX-G250 in metastatic RCC (mRCC) patients. In all, 36 patients with mRCC were included. WX-G250 was given weekly by intravenous infusion for 12 weeks. Patients with stable disease (SD) or response were eligible to receive additional treatment for 8 weeks. None of the 36 enrolled patients experienced any drug-related grade III or IV toxicity. Only three patients had grade II toxicity possibly related to the study medication. In all, 10 patients had SD and received extended treatment. One complete response and a significant regression was observed during the follow-up of the treatment. Five patients with progressive disease at study entry were stable for more than 6 months after study entry. The median survival after treatment start was 15 months. The weekly schedule of WX-G250 was well tolerated. With a median survival of 15 months after the start of this treatment and two late clinical responses, WX-G250 seems to be able to modulate mRCC. To improve the activity of WX-G250-specific antibody-dependent cellular cytotoxicity and the clinical response rate, currently combinations of WX-G250 with cytokines are in phase II trials.

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Section: Discussionmentioning

confidence: 84%

A phase II trial of chimeric monoclonal antibody G250 for advanced renal cell carcinoma patients

Bleumer¹,

Knuth²,

Oosterwijk³

et al. 2004

Br J Cancer

158

View full text Add to dashboard Cite

show abstract

“…All four responding patients have relapsed but are alive at a median follow-up of 41 months whereas only 1 of 14 nonresponding patients are alive. Since activity to second-line cytokines after initial cytokine therapy is rare, 24,25 the durable responses in these cytokine refractory patients offers promise. Nevertheless, patients with good prognostic features have a median survival of 20 months and a 1-year survival of 71%.…”

Section: Discussionmentioning

confidence: 99%

Long-term follow-up of nonmyeloablative allogeneic stem cell transplantation for renal cell carcinoma: The University of Chicago Experience

Artz

Besien

Zimmerman

et al. 2004

Bone Marrow Transplant

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Summary:Nonmyeloablative allogeneic stem cell transplantation (NST) has considerable activity in patients with metastatic renal cell carcinoma (RCC), although there are limited long-term follow-up data. Between February 1999 and May 2003, 18 patients with metastatic RCC underwent 19 matched-sibling NSTs after conditioning with fludarabine and cyclophosphamide with tacrolimus and mycophenolate mofetil as posttransplant immunosuppression. Among the four objective responses, all were partial and have relapsed with a median response duration of 609 days (range, 107-926). All responders are alive at a median of 41 months. Median overall survival for the entire cohort was 14 months. There were four early treatment-related deaths and one late treatment-related death. Eight patients died from progressive disease and five (28%) from treatment-related mortality. Stratifying transplant outcome as early death, intermediate (no response, no early death), or response, the combination of pre-treatment anemia and decreased performance status, was associated with adverse outcome (P ¼ 0.015) and reduced survival (HR 5.4, 95% confidence interval of 1.4 to 21, P ¼ 0.007). Responders demonstrated prolonged survival compared to nonresponders (P ¼ 0.002). NST leads to durable responses in a minority of metastatic RCC patients. Appropriate patient selection is paramount. Anemia and decreased performance status may enable risk stratification.

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“…A large study in 113 patients confirmed the low response (four patients, 3.5%) and stabilisation (13 patients, 11.5%) rates, following a switch from IFNa to IL-2 and from IL-2 to IFNa after failure of the first-line cytokine therapy (Escudier et al, 1999). In the former study (Escudier et al, 1999), none of the patients received the association of both cytokines after one had already failed. In another study (Paolorossi et al, 1995) following the initial work of Lissoni et al (1992), 15 patients received IFNa and vinblastine after failure under IL-2.…”

Section: Discussionmentioning

confidence: 81%

“…Since the start of the study, only two other studies have examined this theme (Paolorossi et al, 1995;Escudier et al, 1999). A large study in 113 patients confirmed the low response (four patients, 3.5%) and stabilisation (13 patients, 11.5%) rates, following a switch from IFNa to IL-2 and from IL-2 to IFNa after failure of the first-line cytokine therapy (Escudier et al, 1999). In the former study (Escudier et al, 1999), none of the patients received the association of both cytokines after one had already failed.…”

Section: Discussionmentioning

confidence: 99%

Subcutaneous interleukin-2, interferon alpha-2b and 5-fluorouracil in metastatic renal cell carcinoma as second-line treatment after failure of previous immunotherapy: a phase II trial

et al. 2003

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The association of interleukin-2 (IL-2), interferon alpha-2a (IFNa), 5-fluorouracil (5-FU) has been reported to induce response in metastatic renal cell carcinoma (MRCC). This study evaluated IL-2, IFNa and 5FU as second-line treatment after failure under immunotherapy. A total of 35 patients received IL-2, at 9 Â 10 6 IU m À2 , once or t.i.d, 5 days a week, every other week. Interferon alpha was administered at 6 MUI, TIW along with IL-2 every week. 5-Fluorouracil was given at 750 mg m À2 day À1 on days 1 -5 every 4 weeks. One cycle lasted 8 weeks. All patients were evaluable for response and toxicity. There were two objective responses (5.7%) and 14 stable diseases (40%). Survival was 14 months. In all, 17 patients experienced grade 3 toxicity. The predictive factor for progression to second-line immunotherapy was the results of first-line immunotherapy, and performance status, delay from primary tumour to metastases and response or stabilisation to chemo-immunotherapy for survival. IL-2, IFNa and 5-FU induce low objective response but stabilisation in patients with MRCC having failed with immunotherapy, and may be considered only in selected patients on performance status, stabilisation or response after first-line immunotherapy and interval from their primary tumour to metastases.

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Cytokines in Metastatic Renal Cell Carcinoma: Is It Useful to Switch to Interleukin-2 or Interferon After Failure of a First Treatment?

Abstract: Cross-over after failure of IL-2 or IFNalpha2a is poorly efficient in metastatic renal cell carcinoma, especially when progression has been clearly documented.

Cited by 85 publications

References 12 publications

A phase II trial of chimeric monoclonal antibody G250 for advanced renal cell carcinoma patients

A phase II trial of chimeric monoclonal antibody G250 for advanced renal cell carcinoma patients

Long-term follow-up of nonmyeloablative allogeneic stem cell transplantation for renal cell carcinoma: The University of Chicago Experience

Subcutaneous interleukin-2, interferon alpha-2b and 5-fluorouracil in metastatic renal cell carcinoma as second-line treatment after failure of previous immunotherapy: a phase II trial

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