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Published in: Cancer Immunology, Immunotherapy 4/2011

01-04-2011 | Original article

Survival after intratumoral interleukin-2 treatment of 72 melanoma patients and response upon the first chemotherapy during follow-up

Authors: Benjamin Weide, Thomas Kurt Eigentler, Annette Pflugfelder, Ulrike Leiter, Friedegund Meier, Jürgen Bauer, Diethard Schmidt, Peter Radny, Claudia Pföhler, Claus Garbe

Published in: Cancer Immunology, Immunotherapy | Issue 4/2011

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Abstract

Systemic high-dose interleukin-2 (IL-2) treatment achieves long-term survival in a subset of advanced patients with melanoma. As we reported previously, intratumoral IL-2 induced complete local responses in more than 60% of melanoma patients. This study aimed to analyze the long-term outcome of 72 patients treated in two prior trials. Melanoma patients (49 stage III, 23 stage IV) with injectable metastases received intratumoral IL-2 injections thrice weekly at individually escalated doses (median duration, 6.5 weeks; median total IL-2 dose, 72 MIU; median number of injected metastases, 10). The observed 2-year overall survival rates were 95.5% for stage III patients with cutaneous metastases only (stage IIIB), 72% for those with combined cutaneous and lymph node involvement (stage IIIC), 66.7% for stage IV patients with disease limited to distant soft-tissue metastases (stage IV M1a), and 9.1% for those with visceral metastases (stage IV M1b and stage IV M1c). Thirty patients who reported recurrence of unresectable distant metastases subsequently received chemotherapy in the further course of disease and showed an overall response rate of 36.7% (16.7% complete responses, 20% partial responses). A high total dose of IL-2 and a dacarbazine/temozolomide-based chemotherapy regimen were variables correlated with a clinical response. In conclusion, patients with cutaneous metastasis without lymph node involvement in stage III and with soft-tissue metastasis without visceral involvement in stage IV showed unexpected favorable survival rates after intratumoral treatment with IL-2. Furthermore, the intratumoral IL-2 treatment seemed to be associated with increased complete and partial responses in subsequent chemotherapies.
Literature
1.
go back to reference Young SE, Martinez SR, Essner R (2006) The role of surgery in treatment of stage IV melanoma. J Surg Oncol 94:344–351PubMedCrossRef Young SE, Martinez SR, Essner R (2006) The role of surgery in treatment of stage IV melanoma. J Surg Oncol 94:344–351PubMedCrossRef
2.
go back to reference Grunhagen DJ, Brunstein F, Graveland WJ, van Geel AN, de Wilt JH, Eggermont AM (2004) One hundred consecutive isolated limb perfusions with TNF-alpha and melphalan in melanoma patients with multiple in-transit metastases. Ann Surg 240:939–947PubMedCrossRef Grunhagen DJ, Brunstein F, Graveland WJ, van Geel AN, de Wilt JH, Eggermont AM (2004) One hundred consecutive isolated limb perfusions with TNF-alpha and melphalan in melanoma patients with multiple in-transit metastases. Ann Surg 240:939–947PubMedCrossRef
3.
4.
go back to reference Eggermont AM, Kirkwood JM (2004) Re-evaluating the role of dacarbazine in metastatic melanoma: what have we learned in 30 years? Eur J Cancer 40:1825–1836PubMedCrossRef Eggermont AM, Kirkwood JM (2004) Re-evaluating the role of dacarbazine in metastatic melanoma: what have we learned in 30 years? Eur J Cancer 40:1825–1836PubMedCrossRef
5.
go back to reference Atkins MB, Lotze MT, Dutcher JP, Fisher RI, Weiss G, Margolin K, Abrams J, Sznol M, Parkinson D, Hawkins M, Paradise C, Kunkel L, Rosenberg SA (1999) High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol 17:2105–2116PubMed Atkins MB, Lotze MT, Dutcher JP, Fisher RI, Weiss G, Margolin K, Abrams J, Sznol M, Parkinson D, Hawkins M, Paradise C, Kunkel L, Rosenberg SA (1999) High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol 17:2105–2116PubMed
6.
go back to reference Gutwald JG, Groth W, Mahrle G (1994) Peritumoral injections of interleukin 2 induce tumour regression in metastatic malignant melanoma. Br J Dermatol 130:541–542PubMedCrossRef Gutwald JG, Groth W, Mahrle G (1994) Peritumoral injections of interleukin 2 induce tumour regression in metastatic malignant melanoma. Br J Dermatol 130:541–542PubMedCrossRef
7.
go back to reference Weide B, Derhovanessian E, Pflugfelder A, Eigentler TK, Radny P, Zelba H, Pfohler C, Pawelec G, Garbe C (2010) High response rate after intratumoral treatment with interleukin-2: results from a phase 2 study in 51 patients with metastasized melanoma. Cancer 116:4139–4146PubMedCrossRef Weide B, Derhovanessian E, Pflugfelder A, Eigentler TK, Radny P, Zelba H, Pfohler C, Pawelec G, Garbe C (2010) High response rate after intratumoral treatment with interleukin-2: results from a phase 2 study in 51 patients with metastasized melanoma. Cancer 116:4139–4146PubMedCrossRef
8.
go back to reference Radny P, Caroli UM, Bauer J, Paul T, Schlegel C, Eigentler TK, Weide B, Schwarz M, Garbe C (2003) Phase II trial of intralesional therapy with interleukin-2 in soft-tissue melanoma metastases. Br J Cancer 89:1620–1626PubMedCrossRef Radny P, Caroli UM, Bauer J, Paul T, Schlegel C, Eigentler TK, Weide B, Schwarz M, Garbe C (2003) Phase II trial of intralesional therapy with interleukin-2 in soft-tissue melanoma metastases. Br J Cancer 89:1620–1626PubMedCrossRef
9.
go back to reference Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 92:205–216PubMedCrossRef Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 92:205–216PubMedCrossRef
10.
go back to reference Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, Buzaid AC, Cochran AJ, Coit DG, Ding S, Eggermont AM, Flaherty KT, Gimotty PA, Kirkwood JM, McMasters KM, Mihm MC Jr, Morton DL, Ross MI, Sober AJ, Sondak VK (2009) Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 27:6199–6206PubMedCrossRef Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, Buzaid AC, Cochran AJ, Coit DG, Ding S, Eggermont AM, Flaherty KT, Gimotty PA, Kirkwood JM, McMasters KM, Mihm MC Jr, Morton DL, Ross MI, Sober AJ, Sondak VK (2009) Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 27:6199–6206PubMedCrossRef
11.
go back to reference Bedikian AY, Millward M, Pehamberger H, Conry R, Gore M, Trefzer U, Pavlick AC, DeConti R, Hersh EM, Hersey P, Kirkwood JM, Haluska FG (2006) Bcl-2 antisense (Oblimersen sodium) plus dacarbazine in patients with advanced melanoma: the Oblimersen melanoma study group. J Clin Oncol 24:4738–4745PubMedCrossRef Bedikian AY, Millward M, Pehamberger H, Conry R, Gore M, Trefzer U, Pavlick AC, DeConti R, Hersh EM, Hersey P, Kirkwood JM, Haluska FG (2006) Bcl-2 antisense (Oblimersen sodium) plus dacarbazine in patients with advanced melanoma: the Oblimersen melanoma study group. J Clin Oncol 24:4738–4745PubMedCrossRef
12.
go back to reference Kaufmann R, Spieth K, Leiter U, Mauch C, von den Driesch P, Vogt T, Linse R, Tilgen W, Schadendorf D, Becker JC, Sebastian G, Krengel S, Kretschmer L, Garbe C, Dummer R (2005) Temozolomide in combination with interferon-alfa versus temozolomide alone in patients with advanced metastatic melanoma: a randomized, phase III, multicenter study from the dermatologic cooperative oncology group. J Clin Oncol 23:9001–9007PubMedCrossRef Kaufmann R, Spieth K, Leiter U, Mauch C, von den Driesch P, Vogt T, Linse R, Tilgen W, Schadendorf D, Becker JC, Sebastian G, Krengel S, Kretschmer L, Garbe C, Dummer R (2005) Temozolomide in combination with interferon-alfa versus temozolomide alone in patients with advanced metastatic melanoma: a randomized, phase III, multicenter study from the dermatologic cooperative oncology group. J Clin Oncol 23:9001–9007PubMedCrossRef
13.
go back to reference Arlen PM, Gulley JL, Parker C, Skarupa L, Pazdur M, Panicali D, Beetham P, Tsang KY, Grosenbach DW, Feldman J, Steinberg SM, Jones E, Chen C, Marte J, Schlom J, Dahut W (2006) A randomized phase II study of concurrent docetaxel plus vaccine versus vaccine alone in metastatic androgen-independent prostate cancer. Clin Cancer Res 12:1260–1269PubMedCrossRef Arlen PM, Gulley JL, Parker C, Skarupa L, Pazdur M, Panicali D, Beetham P, Tsang KY, Grosenbach DW, Feldman J, Steinberg SM, Jones E, Chen C, Marte J, Schlom J, Dahut W (2006) A randomized phase II study of concurrent docetaxel plus vaccine versus vaccine alone in metastatic androgen-independent prostate cancer. Clin Cancer Res 12:1260–1269PubMedCrossRef
14.
go back to reference Davies AM, Evans WK, Mackay JA, Shepherd FA (2004) Treatment of recurrent small cell lung cancer. Hematol Oncol Clin North Am 18:387–416PubMedCrossRef Davies AM, Evans WK, Mackay JA, Shepherd FA (2004) Treatment of recurrent small cell lung cancer. Hematol Oncol Clin North Am 18:387–416PubMedCrossRef
15.
go back to reference Antonia SJ, Mirza N, Fricke I, Chiappori A, Thompson P, Williams N, Bepler G, Simon G, Janssen W, Lee JH, Menander K, Chada S, Gabrilovich DI (2006) Combination of p53 cancer vaccine with chemotherapy in patients with extensive stage small cell lung cancer. Clin Cancer Res 12:878–887PubMedCrossRef Antonia SJ, Mirza N, Fricke I, Chiappori A, Thompson P, Williams N, Bepler G, Simon G, Janssen W, Lee JH, Menander K, Chada S, Gabrilovich DI (2006) Combination of p53 cancer vaccine with chemotherapy in patients with extensive stage small cell lung cancer. Clin Cancer Res 12:878–887PubMedCrossRef
16.
go back to reference Wheeler CJ, Das A, Liu G, Yu JS, Black KL (2004) Clinical responsiveness of glioblastoma multiforme to chemotherapy after vaccination. Clin Cancer Res 10:5316–5326PubMedCrossRef Wheeler CJ, Das A, Liu G, Yu JS, Black KL (2004) Clinical responsiveness of glioblastoma multiforme to chemotherapy after vaccination. Clin Cancer Res 10:5316–5326PubMedCrossRef
17.
go back to reference Gribben JG, Ryan DP, Boyajian R, Urban RG, Hedley ML, Beach K, Nealon P, Matulonis U, Campos S, Gilligan TD, Richardson PG, Marshall B, Neuberg D, Nadler LM (2005) Unexpected association between induction of immunity to the universal tumor antigen CYP1B1 and response to next therapy. Clin Cancer Res 11:4430–4436PubMedCrossRef Gribben JG, Ryan DP, Boyajian R, Urban RG, Hedley ML, Beach K, Nealon P, Matulonis U, Campos S, Gilligan TD, Richardson PG, Marshall B, Neuberg D, Nadler LM (2005) Unexpected association between induction of immunity to the universal tumor antigen CYP1B1 and response to next therapy. Clin Cancer Res 11:4430–4436PubMedCrossRef
18.
go back to reference Chiappori AA, Soliman H, Janssen WE, Antonia SJ, Gabrilovich DI (2010) INGN-225: a dendritic cell-based p53 vaccine (Ad.p53-DC) in small cell lung cancer: observed association between immune response and enhanced chemotherapy effect. Expert Opin Biol Ther 10:983–991PubMedCrossRef Chiappori AA, Soliman H, Janssen WE, Antonia SJ, Gabrilovich DI (2010) INGN-225: a dendritic cell-based p53 vaccine (Ad.p53-DC) in small cell lung cancer: observed association between immune response and enhanced chemotherapy effect. Expert Opin Biol Ther 10:983–991PubMedCrossRef
19.
go back to reference Gabrilovich DI (2007) Combination of chemotherapy and immunotherapy for cancer: a paradigm revisited. Lancet Oncol 8:2–3PubMedCrossRef Gabrilovich DI (2007) Combination of chemotherapy and immunotherapy for cancer: a paradigm revisited. Lancet Oncol 8:2–3PubMedCrossRef
20.
go back to reference Maas RA, Van Weering DH, Dullens HF, Den Otter W (1991) Intratumoral low-dose interleukin-2 induces rejection of distant solid tumour. Cancer Immunol Immunother 33:389–394PubMedCrossRef Maas RA, Van Weering DH, Dullens HF, Den Otter W (1991) Intratumoral low-dose interleukin-2 induces rejection of distant solid tumour. Cancer Immunol Immunother 33:389–394PubMedCrossRef
21.
go back to reference Van Es RJ, Baselmans AH, Koten JW, Van Dijk JE, Koole R, Den Otter W (2000) Perilesional IL-2 treatment of a VX2 head-and-neck cancer model can induce a systemic anti-tumour activity. Anticancer Res 20:4163–4170PubMed Van Es RJ, Baselmans AH, Koten JW, Van Dijk JE, Koole R, Den Otter W (2000) Perilesional IL-2 treatment of a VX2 head-and-neck cancer model can induce a systemic anti-tumour activity. Anticancer Res 20:4163–4170PubMed
22.
go back to reference Neville ME, Robb RJ, Popescu MC (2001) In situ vaccination against a non-immunogenic tumour using intratumoural injections of liposomal interleukin 2. Cytokine 16:239–250PubMedCrossRef Neville ME, Robb RJ, Popescu MC (2001) In situ vaccination against a non-immunogenic tumour using intratumoural injections of liposomal interleukin 2. Cytokine 16:239–250PubMedCrossRef
23.
go back to reference Rosenberg SA, Yannelli JR, Yang JC, Topalian SL, Schwartzentruber DJ, Weber JS, Parkinson DR, Seipp CA, Einhorn JH, White DE (1994) Treatment of patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and interleukin 2. J Natl Cancer Inst 86:1159–1166PubMedCrossRef Rosenberg SA, Yannelli JR, Yang JC, Topalian SL, Schwartzentruber DJ, Weber JS, Parkinson DR, Seipp CA, Einhorn JH, White DE (1994) Treatment of patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and interleukin 2. J Natl Cancer Inst 86:1159–1166PubMedCrossRef
24.
go back to reference Rosenberg SA, Yang JC, Topalian SL, Schwartzentruber DJ, Weber JS, Parkinson DR, Seipp CA, Einhorn JH, White DE (1994) Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA 271:907–913PubMedCrossRef Rosenberg SA, Yang JC, Topalian SL, Schwartzentruber DJ, Weber JS, Parkinson DR, Seipp CA, Einhorn JH, White DE (1994) Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA 271:907–913PubMedCrossRef
25.
go back to reference Phan GQ, Attia P, Steinberg SM, White DE, Rosenberg SA (2001) Factors associated with response to high-dose interleukin-2 in patients with metastatic melanoma. J Clin Oncol 19:3477–3482PubMed Phan GQ, Attia P, Steinberg SM, White DE, Rosenberg SA (2001) Factors associated with response to high-dose interleukin-2 in patients with metastatic melanoma. J Clin Oncol 19:3477–3482PubMed
26.
go back to reference Denucci CC, Mitchell JS, Shimizu Y (2009) Integrin function in T-cell homing to lymphoid and nonlymphoid sites: getting there and staying there. Crit Rev Immunol 29:87–109PubMed Denucci CC, Mitchell JS, Shimizu Y (2009) Integrin function in T-cell homing to lymphoid and nonlymphoid sites: getting there and staying there. Crit Rev Immunol 29:87–109PubMed
Metadata
Title
Survival after intratumoral interleukin-2 treatment of 72 melanoma patients and response upon the first chemotherapy during follow-up
Authors
Benjamin Weide
Thomas Kurt Eigentler
Annette Pflugfelder
Ulrike Leiter
Friedegund Meier
Jürgen Bauer
Diethard Schmidt
Peter Radny
Claudia Pföhler
Claus Garbe
Publication date
01-04-2011
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 4/2011
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-010-0957-3

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