Phase II trial of bryostatin-1 in combination with cisplatin in patients with recurrent or persistent epithelial ovarian cancer: a California cancer consortium study (original) (raw)

Summary

Background The California Cancer Consortium has performed a Phase II trial of infusional bryostatin, a protein kinase C inhibitor isolated from the marine invertebrate bryozoan, Bugula Neritina, a member of the phylum Ectoprocta, in combination with cisplatin, in patients (pts) with recurrent platinum-sensitive or resistant ovarian cancer (OC). Methods Pts received bryostatin 45 mcg/m2 as a 72 h continuous infusion followed by cisplatin 50 mg/m2. Cycles were repeated every 3 weeks. Dosages were chosen based on phase I data obtained by the CCC in a population of pts with mixed tumor types. Results Eight pts with recurrent or persistent epithelial OC received 23 cycles of treatment. All pts had received previous platinum-based chemotherapy; two pts had received one prior course, five had received two prior courses, and one had received three prior courses of chemotherapy. The median age was 64 (range 32–72), and Karnofsky performance status 90 (range 80–100). A median of 3 cycles of chemotherapy were delivered (range: 1–5). The median progression-free and overall survivals were 3 and 8.2 months respectively. Best responses included two partial responses (one in a platinum-resistant pt), three pts with stable disease, and three progressions. All pts experienced Grade 3 or 4 toxicities including severe myalgias/pain/fatigue/asthenia in six pts, and severe nausea/vomiting/constipation in two other pts. One pt experienced a seizure and liver function tests were elevated in one other. Conclusions A modest response rate is observed in pts with recurrent or persistent ovarian cancer treated with the combination of bryostatin and cisplatin. The toxicity profile, however, observed in this pt population (primarily severe myalgias), precludes tolerability and prevents this combination from further investigation at this dose and schedule. It is possible that platinum pre-exposure in OC patients exacerbates observed toxicity. Phase II dosages of investigational agents in OC pts that are determined by phase I trials in pts with other tumor types should be chosen cautiously.

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Author notes

  1. James H. Doroshow
    Present address: Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA

Authors and Affiliations

  1. Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, 1500 E Duarte Rd, Duarte, CA, 91010, USA
    Robert J. Morgan Jr, Lucille Leong, Warren Chow & James H. Doroshow
  2. University of California, Davis, Davis, CA, USA
    David Gandara
  3. Department of Biostatistics, City of Hope National Medical Center, Duarte, CA, 91010, USA
    Paul Frankel
  4. University of Southern California, Los Angeles, CA, USA
    Agustin Garcia & Heinz-Josef Lenz

Authors

  1. Robert J. Morgan Jr
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  2. Lucille Leong
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  3. Warren Chow
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  4. David Gandara
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  5. Paul Frankel
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  6. Agustin Garcia
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  7. Heinz-Josef Lenz
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  8. James H. Doroshow
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Corresponding author

Correspondence toRobert J. Morgan Jr.

Additional information

Reported in abstract form in: Proc. Amer. Soc. Clin. Oncol. 23:5140, 2005.

Supported by NCI Cancer Center Core Grant CA 33572, CA 63265, and CA 62505 from the NCI and NCI Contract N01-CM-17101.

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Morgan, R.J., Leong, L., Chow, W. et al. Phase II trial of bryostatin-1 in combination with cisplatin in patients with recurrent or persistent epithelial ovarian cancer: a California cancer consortium study.Invest New Drugs 30, 723–728 (2012). https://doi.org/10.1007/s10637-010-9557-5

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