Literature DB >> 14586215

A phase II study of rebeccamycin analog (NSC-655649) in metastatic renal cell cancer.

Maha Hussain1, Ulka Vaishampayan, Lance K Heilbrun, Vikash Jain, Patricia M LoRusso, Percy Ivy, Lawrence Flaherty.   

Abstract

OBJECTIVE: Rebeccamycin analog (NSC-655649) is an antibiotic with antitumor properties demonstrated in preclinical and phase I studies. We conducted a phase II trial to evaluate the efficacy and toxicity of this agent in patients with advanced renal cell cancer (RCC).
METHODS: Eligible patients had histologically or cytologically confirmed diagnosis of RCC that was either locally advanced unresectable, locally recurrent, or metastatic. Patients had to have measurable disease, no prior chemotherapy, life expectancy of greater than 12 weeks, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, adequate-organ function, and be >/=18 years old. Patients were treated with NSC-655649 at a dose of 165 mg/m(2) daily i.v. over 30-60 min for 5 days. Treatment was repeated every 21 days. Response was assessed every two courses.
RESULTS: Twenty-four patients were enrolled. There were sixteen males and eight females with a median age of 60.5 years (range 42-76). Nineteen were Caucasians, seventeen had prior nephrectomy, and thirteen had prior immunotherapy. The major toxicity was myelosuppression with grade 3 and 4 neutropenia in 38% of patients and anemia in 33% of patients. There were two partial responses (2/24, 8%) and 11 patients (46%) achieved stable disease (SD). The 6-month progression-free rate for patients with SD was 30%. Of the seventeen patients with progressive disease at registration, one had a PR and eight had SD. The overall median survival time for all 24 patients was 10.0 months (90% CI=5.2, 17.4 months). The 12-month survival rate was 39%, with 90% CI=(0.21, 0.58). Nine patients are still alive with survival times ranging from 3.8 to 24.2 months, at a median follow-up time of 11.9 months.
CONCLUSION: Rebeccamycin analog (NSC-655649) is well tolerated and has modest antitumor activity in patients with advanced RCC.

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Year:  2003        PMID: 14586215     DOI: 10.1023/a:1026259503954

Source DB:  PubMed          Journal:  Invest New Drugs        ISSN: 0167-6997            Impact factor:   3.850


  9 in total

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9.  Phase I clinical and pharmacokinetic study of NSC 655649, a rebeccamycin analogue, given in both single-dose and multiple-dose formats.

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Journal:  Clin Cancer Res       Date:  2002-07       Impact factor: 12.531

  9 in total
  5 in total

1.  Rebeccamycin analog for refractory breast cancer: a randomized phase II trial of dosing schedules.

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Journal:  Invest New Drugs       Date:  2006-09-13       Impact factor: 3.850

2.  Robust in vitro activity of RebF and RebH, a two-component reductase/halogenase, generating 7-chlorotryptophan during rebeccamycin biosynthesis.

Authors:  Ellen Yeh; Sylvie Garneau; Christopher T Walsh
Journal:  Proc Natl Acad Sci U S A       Date:  2005-03-02       Impact factor: 11.205

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Authors:  Robert W Robey; Tomasz Obrzut; Suneet Shukla; Orsolya Polgar; Sira Macalou; Julian C Bahr; Attilio Di Pietro; Suresh V Ambudkar; Susan E Bates
Journal:  Cancer Chemother Pharmacol       Date:  2009-01-09       Impact factor: 3.333

Review 4.  Camptothecin and podophyllotoxin derivatives: inhibitors of topoisomerase I and II - mechanisms of action, pharmacokinetics and toxicity profile.

Authors:  Jörg T Hartmann; Hans-Peter Lipp
Journal:  Drug Saf       Date:  2006       Impact factor: 5.606

5.  The cell competition-based high-throughput screening identifies small compounds that promote the elimination of RasV12-transformed cells from epithelia.

Authors:  Hajime Yamauchi; Takanori Matsumaru; Tomoko Morita; Susumu Ishikawa; Katsumi Maenaka; Ichigaku Takigawa; Kentaro Semba; Shunsuke Kon; Yasuyuki Fujita
Journal:  Sci Rep       Date:  2015-10-20       Impact factor: 4.379

  5 in total

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