Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma: the Oblimersen Melanoma Study Group.

@article{Bedikian2006Bcl2A,
  title={Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma: the Oblimersen Melanoma Study Group.},
  author={Agop Y. Bedikian and Michael Millward and Hubert Pehamberger and Robert M. Conry and Martin. E. Gore and Uwe Trefzer and Anna C. Pavlick and Ronald C. Deconti and Evan M. Hersh and Peter Hersey and John M. Kirkwood and Frank G. Haluska},
  journal={Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
  year={2006},
  volume={24 29},
  pages={
          4738-45
        },
  url={https://api.semanticscholar.org/CorpusID:24845701}
}
The addition of oblimersen to dacarbazine significantly improved multiple clinical outcomes in patients with advanced melanoma and increased overall survival in patients without an elevated baseline serum LDH.
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612 Citations

Dacarbazine with or without oblimersen (a Bcl-2 antisense oligonucleotide) in chemotherapy-naive patients with advanced melanoma and low–normal serum lactate dehydrogenase: ‘The AGENDA trial’

The addition of oblimersen to Dac did not significantly improve overall survival nor progression-free survival in patients with advanced melanoma and low–normal levels of LDH at baseline.

Docetaxel plus oblimersen sodium (Bcl-2 antisense oligonucleotide): an EORTC multicenter, randomized phase II study in patients with castration-resistant prostate cancer.

Oblimersen added to docetaxel was associated with an increase in the incidence of grade > or = 3 fatigue, mucositis, and thrombocytopenia and the primary end points of the study were not met.

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

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

Oblimersen in the treatment of metastatic melanoma.

The biochemistry, pharmacodynamics and pharmacokinetics, safety and efficacy data related to oblimersen in melanoma are reviewed, showing that the addition of oblim Andersen to dacarbazine significantly improved multiple clinical outcomes relative to dAcarbazine alone.

Randomized phase II Study of carboplatin and etoposide with or without the bcl-2 antisense oligonucleotide oblimersen for extensive-stage small-cell lung cancer: CALGB 30103.

Despite extensive data supporting a critical role for Bcl-2 in chemoresistance in SCLC, addition of oblimersen to a standard regimen for this disease did not improve any clinical outcome measure.

Phase I trial of oblimersen (Genasense®) and gemcitabine in refractory and advanced malignancies

The maximum tolerated dose levels of oblimersen and gemcitabine in combination were well tolerated, and a formal MTD was not determined, and there was a correlation between Bcl-2 reduction and stable disease.

Oblimersen combined with docetaxel, adriamycin and cyclophosphamide as neo-adjuvant systemic treatment in primary breast cancer: final results of a multicentric phase I study.

Oblimersen up to a dose of 7 mg/kg/day administered as a 24-h infusion on days 1-7 can be safely administered in combination with standard TAC on day 5 as NST in patients with PBC and the safety and preliminary efficacy warrants further evaluation.

A phase II trial of bevacizumab with dacarbazine and daily low-dose interferon-α2a as first line treatment in metastatic melanoma

There was a trend towards favourable PFS among patients with only minimal or moderate change in these marker expression levels, and the present regimen was active in this patient group but was also associated with remarkable vascular events.

A phase II multicenter study of ipilimumab with or without dacarbazine in chemotherapy-naïve patients with advanced melanoma

Ipilimumab therapy resulted in clinically meaningful responses in advanced melanoma patients, and the results support further investigations of ipilimumAB in combination with DTIC.

BEAM: a randomized phase II study evaluating the activity of bevacizumab in combination with carboplatin plus paclitaxel in patients with previously untreated advanced melanoma.

The study did not meet the primary objective of statistically significant improvement in PFS with the addition of bevacizumab to carboplatin plus paclitaxel in patients with previously untreated metastatic melanoma.
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19 References

Chemosensitisation of malignant melanoma by BCL2 antisense therapy

Prospective Randomized Comparison of Dacarbazine (DTIC) Versus DTIC Plus Interferon-Alpha (IFN-α) in Metastatic Melanoma

This study failed to demonstrate a survival benefit for patients receiving IFN-α in combination with DTIC, and a meta-analysis is required to determine whether there is a role for the addition of IFn-α to DTIC in the treatment of this disease.

Sequential biochemotherapy versus chemotherapy for metastatic melanoma: results from a phase III randomized trial.

Cytokines substantially augment the antitumor activity of chemotherapy at the expense of considerable toxicity in patients with metastatic melanoma.

Oblimersen Bcl-2 antisense: facilitating apoptosis in anticancer treatment.

A growing body of preclinical and clinical evidence suggests that oblimersen synergizes with many cytotoxic and biologic/immunotherapeutic agents against a variety of hematologic malignancies and solid tumors.

Phase III trial of dacarbazine versus dacarbazine with interferon alpha-2b versus dacarbazine with tamoxifen versus dacarbazine with interferon alpha-2b and tamoxifen in patients with metastatic malignant melanoma: an Eastern Cooperative Oncology Group study.

Neither IFN, TMX, nor the combination significantly improved the response rate, time to treatment failure, overall survival, or survival when added to dacarbazine, but IFN significantly increased toxicity.

Prospective randomized trial of the treatment of patients with metastatic melanoma using chemotherapy with cisplatin, dacarbazine, and tamoxifen alone or in combination with interleukin-2 and interferon alfa-2b.

The use of combination chemoimmunotherapy regimens is not recommended in the absence of well-designed, prospective, randomized protocols showing the benefit of this treatment strategy.

Phase II randomized study of dacarbazine, carmustine, cisplatin and tamoxifen versus dacarbazine alone in advanced melanoma patients

The overall response rate obtained with DBDT was greater than that obtained with DTIC alone; however, this combination increases toxicity with limited impact on overall survival.

Dacarbazine-based chemotherapy for metastatic melanoma: thirty-year experience overview.

Current status of DTIC single agent and DTIC-based combination chemotherapy has been extensively reviewed and the better understanding of the mechanisms responsible for melanoma chemoresistance and the development of new therapeutical strategies could change the scenario in the next future.

Phase III multicenter randomized trial of the Dartmouth regimen versus dacarbazine in patients with metastatic melanoma.

There was no difference in survival time and only a small, statistically nonsignificant increase in tumor response for stage IV melanoma patients treated with the Dartmouth regimen compared with dacarbazine.

Combination chemotherapy with or without s.c. IL-2 and IFN-α: results of a prospectively randomized trial of the Cooperative Advanced Malignant Melanoma Chemoimmunotherapy Group (ACIMM)

There was no significant difference in median progression free survival and in median overall survival for combined chemoimmunotherapy and for chemotherapy, respectively.