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01.01.2013 | Original Article

Oblimersen in combination with temozolomide and albumin-bound paclitaxel in patients with advanced melanoma: a phase I trial

verfasst von: Patrick A. Ott, Jason Chang, Kathleen Madden, Rajni Kannan, Caroline Muren, Crystal Escano, Xin Cheng, Yongzhao Shao, Sandra Mendoza, Alex Gandhi, Leonard Liebes, Anna C. Pavlick

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 1/2013

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Abstract

Purpose

The combination of oblimersen, a bcl-2 antisense oligonucleotide, and dacarbazine lead to superior progression-free survival in advanced melanoma patients. Albumin-bound paclitaxel (nab-paclitaxel) has single-agent activity in melanoma.

Methods

In a phase I trial, chemotherapy-naïve patients with metastatic melanoma and normal LDH levels were enrolled on 3 cohorts. The treatment regimen consisted of 56-day cycles of oblimersen (7 mg/kg/day continuous IV infusion on day 1–7 and 22–28 in cohort 1 and 2; 900 mg fixed dose, twice weekly in weeks 1–2, 4–5 for cohort 3), temozolomide (75 mg/m², days 1–42), and nab-paclitaxel (175 mg/m² in cohort 1 and 3, 260 mg/m² in cohort 2 on day 7 and 28). Apoptosis markers were tested in pre- and post-treatment specimens of a subset of patients.

Results

Six grade 3 events (neutropenia, renal insufficiency, hyponatremia, elevated creatinine, allergic reaction, and neuropathy) and 2 grade 4 events (neutropenia and thrombocytopenia) were seen in 32 patients. The objective response rate was 40.6 % (2 complete responses and 11 partial responses) and 11 patients had stable disease, for a disease control rate of 75 %.

Conclusions

The combination of oblimersen, temozolomide, and nab-paclitaxel was well tolerated and demonstrated encouraging activity in patients with advanced melanoma.

Albert VA, Koh HK, Geller AC, Miller DR, Prout MN, Lew RA (1990) Years of potential life lost: another indicator of the impact of cutaneous malignant melanoma on society. J Am Acad Dermatol 23(2 Pt 1):308–310PubMedCrossRef

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(29):4738–4745. doi:10.1200/JCO.2006.06.0483 PubMedCrossRef

Chapman PB, Einhorn LH, Meyers ML, Saxman S, Destro AN, Panageas KS, Begg CB, Agarwala SS, Schuchter LM, Ernstoff MS, Houghton AN, Kirkwood JM (1999) Phase III multicenter randomized trial of the Dartmouth regimen versus dacarbazine in patients with metastatic melanoma. J Clin Oncol 17(9):2745–2751PubMed

Middleton MR, Grob JJ, Aaronson N, Fierlbeck G, Tilgen W, Seiter S, Gore M, Aamdal S, Cebon J, Coates A, Dreno B, Henz M, Schadendorf D, Kapp A, Weiss J, Fraass U, Statkevich P, Muller M, Thatcher N (2000) Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol 18(1):158–166PubMed

Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, Dummer R, Garbe C, Testori A, Maio M, Hogg D, Lorigan P, Lebbe C, Jouary T, Schadendorf D, Ribas A, O’Day SJ, Sosman JA, Kirkwood JM, Eggermont AM, Dreno B, Nolop K, Li J, Nelson B, Hou J, Lee RJ, Flaherty KT, McArthur AG (2011) Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 364(26):2507–2516. doi:10.1056/NEJMoa1103782 PubMedCrossRef

Flaherty KT, Puzanov I, Kim KB, Ribas A, McArthur GA, Sosman JA, O’Dwyer PJ, Lee RJ, Grippo JF, Nolop K, Chapman PB (2010) Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med 363(9):809–819. doi:10.1056/NEJMoa1002011 PubMedCrossRef

Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363(8):711–723. doi:10.1056/NEJMoa1003466 PubMedCrossRef

Robert C, Thomas L, Bondarenko I, O’Day S, M DJ, Garbe C, Lebbe C, Baurain JF, Testori A, Grob JJ, Davidson N, Richards J, Maio M, Hauschild A, Miller WH, Jr., Gascon P, Lotem M, Harmankaya K, Ibrahim R, Francis S, Chen TT, Humphrey R, Hoos A, Wolchok JD (2011) Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 364 (26):2517–2526. doi:10.1056/NEJMoa1104621

Carvajal RD, Antonescu CR, Wolchok JD, Chapman PB, Roman RA, Teitcher J, Panageas KS, Busam KJ, Chmielowski B, Lutzky J, Pavlick AC, Fusco A, Cane L, Takebe N, Vemula S, Bouvier N, Bastian BC, Schwartz GK (2011) KIT as a therapeutic target in metastatic melanoma. JAMA 305(22):2327–2334. doi:10.1001/jama.2011.746 PubMedCrossRef

10.

Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366(26):2455–2465. doi:10.1056/NEJMoa1200694 PubMedCrossRef

11.

Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, Dummer R, Garbe C, Testori A, Maio M, Hogg D, Lorigan P, Lebbe C, Jouary T, Schadendorf D, Ribas A, O’Day SJ, Sosman JA, Kirkwood JM, Eggermont AM, Dreno B, Nolop K, Li J, Nelson B, Hou J, Lee RJ, Flaherty KT, McArthur GA (2011) Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 364(26):2507–2516. doi:10.1056/NEJMoa1103782 PubMedCrossRef

12.

Flaherty KT, Robert C, Hersey P, Nathan P, Garbe C, Milhem M, Demidov LV, Hassel JC, Rutkowski P, Mohr P, Dummer R, Trefzer U, Larkin JM, Utikal J, Dreno B, Nyakas M, Middleton MR, Becker JC, Casey M, Sherman LJ, Wu FS, Ouellet D, Martin AM, Patel K, Schadendorf D (2012) Improved Survival with MEK Inhibition in BRAF-Mutated Melanoma. N Engl J Med. doi:10.1056/NEJMoa1203421

13.

Sosman JA, Kim KB, Schuchter L, Gonzalez R, Pavlick AC, Weber JS, McArthur GA, Hutson TE, Moschos SJ, Flaherty KT, Hersey P, Kefford R, Lawrence D, Puzanov I, Lewis KD, Amaravadi RK, Chmielowski B, Lawrence HJ, Shyr Y, Ye F, Li J, Nolop KB, Lee RJ, Joe AK, Ribas A (2012) Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med 366(8):707–714. doi:10.1056/NEJMoa1112302 PubMedCrossRef

14.

Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366(26):2443–2454. doi:10.1056/NEJMoa1200690 PubMedCrossRef

15.

Margolin KA, Liu PY, Flaherty LE, Sosman JA, Walker MJ, Smith JW 3rd, Fletcher WS, Weiss GR, Unger JM, Sondak VK (1998) Phase II study of carmustine, dacarbazine, cisplatin, and tamoxifen in advanced melanoma: a Southwest Oncology Group study. J Clin Oncol 16(2):664–669PubMed

16.

McClay EF, Mastrangelo MJ, Berd D, Bellet RE (1992) Effective combination chemo/hormonal therapy for malignant melanoma: experience with three consecutive trials. Int J Cancer 50(4):553–556PubMedCrossRef

17.

Hofmann MA, Gabriel V, Milling A, Kiecker F, Sterry W, Trefzer U (2007) High-dose platinum combination therapy in pretreated patients with disseminated melanoma. Chemotherapy 53(6):422–428PubMedCrossRef

18.

Azmi AS, Wang Z, Philip PA, Mohammad RM, Sarkar FH (2011) Emerging Bcl-2 inhibitors for the treatment of cancer. Expert Opin Emerg Drugs 16(1):59–70. doi:10.1517/14728214.2010.515210 PubMedCrossRef

19.

Soengas MS, Lowe SW (2003) Apoptosis and melanoma chemoresistance. Oncogene 22(20):3138–3151. doi:10.1038/sj.onc.1206454 PubMedCrossRef

20.

Jansen B, Schlagbauer-Wadl H, Brown BD, Bryan RN, van Elsas A, Muller M, Wolff K, Eichler HG, Pehamberger H (1998) bcl-2 antisense therapy chemosensitizes human melanoma in SCID mice. Nat Med 4(2):232–234PubMedCrossRef

21.

Bush JA, Li G (2003) The role of Bcl-2 family members in the progression of cutaneous melanoma. Clin Exp Metastasis 20(6):531–539PubMedCrossRef

22.

Divito KA, Berger AJ, Camp RL, Dolled-Filhart M, Rimm DL, Kluger HM (2004) Automated quantitative analysis of tissue microarrays reveals an association between high Bcl-2 expression and improved outcome in melanoma. Cancer Res 64(23):8773–8777. doi:10.1158/0008-5472.CAN-04-1387 PubMedCrossRef

23.

Jansen B, Wacheck V, Heere-Ress E, Schlagbauer-Wadl H, Hoeller C, Lucas T, Hoermann M, Hollenstein U, Wolff K, Pehamberger H (2000) Chemosensitisation of malignant melanoma by BCL2 antisense therapy. Lancet 356(9243):1728–1733. doi:10.1016/S0140-6736(00)03207-4 PubMedCrossRef

24.

Hersh EM, O’Day SJ, Ribas A, Samlowski WE, Gordon MS, Shechter DE, Clawson AA, Gonzalez R (2010) A phase 2 clinical trial of nab-paclitaxel in previously treated and chemotherapy-naive patients with metastatic melanoma. Cancer 116(1):155–163. doi:10.1002/cncr.24720 PubMed

25.

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. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92(3):205–216PubMedCrossRef

26.

Balch CM, Buzaid AC, Soong SJ, Atkins MB, Cascinelli N, Coit DG, Fleming ID, Gershenwald JE, Houghton A Jr, Kirkwood JM, McMasters KM, Mihm MF, Morton DL, Reintgen DS, Ross MI, Sober A, Thompson JA, Thompson JF (2001) Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 19(16):3635–3648PubMed

27.

Bafaloukos D, Gogas H, Georgoulias V, Briassoulis E, Fountzilas G, Samantas E, Kalofonos C, Skarlos D, Karabelis A, Kosmidis P (2002) Temozolomide in combination with docetaxel in patients with advanced melanoma: a phase II study of the Hellenic Cooperative Oncology Group. J Clin Oncol 20(2):420–425PubMedCrossRef

28.

Flaherty KT, Lee SJ, Schuchter LM, Flaherty LE, Wright JJ, Leming PD, Kirkwood JM (2010) Final results of E2603: A double-blind, randomized phase III trial comparing carboplatin ©/paclitaxel (P) with or without sorafenib (S) in metastatic melanoma. In: 2010 ASCO Annual Meeting, Chicago, 2010

29.

Korn EL, Liu PY, Lee SJ, Chapman JA, Niedzwiecki D, Suman VJ, Moon J, Sondak VK, Atkins MB, Eisenhauer EA, Parulekar W, Markovic SN, Saxman S, Kirkwood JM (2008) Meta-analysis of phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future phase II trials. J Clin Oncol 26(4):527–534. doi:10.1200/JCO.2007.12.7837 PubMedCrossRef

Titel: Oblimersen in combination with temozolomide and albumin-bound paclitaxel in patients with advanced melanoma: a phase I trial
verfasst von: Patrick A. Ott
Jason Chang
Kathleen Madden
Rajni Kannan
Caroline Muren
Crystal Escano
Xin Cheng
Yongzhao Shao
Sandra Mendoza
Alex Gandhi
Leonard Liebes
Anna C. Pavlick
Publikationsdatum: 01.01.2013
Verlag: Springer-Verlag
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 1/2013
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-012-1995-7

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Oblimersen in combination with temozolomide and albumin-bound paclitaxel in patients with advanced melanoma: a phase I trial

Abstract

Purpose

Methods

Results

Conclusions

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Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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