Phase I trial of Triapine-Cisplatin-Paclitaxel chemotherapy for advanced stage or metastatic solid tumor cancers

Charles A. Kunos, Edward Chu, Della F. Makower, Andreas Kaubisch, Mario Sznol, Susan Percy Ivy

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Ribonucleotide reductase (RNR) is an enzyme involved in the de novo synthesis of deoxyribonucleotides, which are critical for DNA replication and DNA repair. Triapine is a small-molecule RNR inhibitor. A phase I trial studied the safety of triapine in combination with cisplatin-paclitaxel in patients with advanced stage or metastatic solid tumor cancers in an effort to capitalize on disrupted DNA damage repair. A total of 13 patients with various previously treated cancers were given a 96-h continuous intravenous (i.v.) infusion of triapine (40-120 mg/m2) on day 1, and then 3-h i.v. paclitaxel (80 mg/m2) followed by 1-h i.v. cisplatin (50-75 mg/m2) on day 3. This combination regimen was repeated every 21 days. The maximum tolerated dose (MTD) for each agent was identified to be triapine (80 mg/m2), cisplatin (50 mg/m2), and paclitaxel (80 mg/m2). Common grade 3 or 4 toxicities included reversible anemia, leukopenia, thrombocytopenia, or electrolyte abnormalities. The combination regimen of triapine-cisplatin-paclitaxel resulted in no objective responses; however, five (83%) of six patients treated at the MTD had stable disease between 1 and 8 months duration. This phase I study showed that the combination regimen of triapine-cisplatin-paclitaxel was safe and provides a rational basis for a follow-up phase II trial to evaluate efficacy and progression-free survival in women with metastatic or recurrent uterine cervix cancer.

Original languageEnglish (US)
Article number62
JournalFrontiers in Oncology
Volume7
Issue numberAPR
DOIs
StatePublished - Apr 4 2017

Fingerprint

Drug Therapy
Ribonucleotide Reductases
Neoplasms
Maximum Tolerated Dose
Paclitaxel
DNA Repair
Cisplatin
Deoxyribonucleotides
Leukopenia
DNA Replication
Intravenous Infusions
Uterine Cervical Neoplasms
Thrombocytopenia
Electrolytes
DNA Damage
Disease-Free Survival
3-aminopyridine-2-carboxaldehyde thiosemicarbazone
TP protocol
Anemia
Safety

Keywords

  • Cancer
  • Cervical cancer
  • Cisplatin
  • Maximum tolerated dose
  • Paclitaxel
  • Phase I clinical trial
  • Triapine
  • Uterine cervix cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Phase I trial of Triapine-Cisplatin-Paclitaxel chemotherapy for advanced stage or metastatic solid tumor cancers. / Kunos, Charles A.; Chu, Edward; Makower, Della F.; Kaubisch, Andreas; Sznol, Mario; Percy Ivy, Susan.

In: Frontiers in Oncology, Vol. 7, No. APR, 62, 04.04.2017.

Research output: Contribution to journalArticle

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