Dose escalation of paclitaxel with high-dose cyclophosphamide, with analysis of progenitor-cell mobilization and hematologic support of advanced ovarian cancer patients receiving rapidly sequenced high-dose carboplatin/cyclophosphamide courses Journal Article


Authors: Fennelly, D.; Schneider, J.; Spriggs, D.; Bengala, C.; Hakes, T.; Reich, L.; Barakat, R.; Curtin, J.; Moore, M. A. S.; Hoskins, W.; Norton, L.; Crown, J.
Article Title: Dose escalation of paclitaxel with high-dose cyclophosphamide, with analysis of progenitor-cell mobilization and hematologic support of advanced ovarian cancer patients receiving rapidly sequenced high-dose carboplatin/cyclophosphamide courses
Abstract: Purpose: We commenced a phase I study of escalating-dose Taxol (paclitaxel; Bristol-Myers Squibb Co, Wallingford, CT) in addition to cyclophosphamide, to assess its impact on both antitumor efficacy and mobilization of peripheral-blood progenitor cells (PBP). Patients and Methods: Induction therapy consisted of two cycles of cyclophosphamide 3.0 g/m2 plus escalating-dose Taxol (dose levels I to IV, 150, 200, 250, and 300 mg/m2, respectively) in cohorts of three, plus filgrastim granulocyte colony-stimulating factor [G-CSF]) and leukaphereses to harvest PBP, followed by four courses of rapidly cycled carboplatin and cyclophosphamide (1,000 and 1,500 mg/m2 per course, respectively), for which hematopoietic rescue was achieved with PBP. Results: Sixteen patients completed all planned cycles of Taxol/cyclophosphamide. Fifty-four cycles of carboplatin/cyclophosphamide were given and rescued with PBP. The median interval between treatments for Taxol/cyclophosphamide courses was 14 days (range, 13 to 21). Twelve patients completed all planned cycles of carboplatin/cyclophosphamide. The median intertreatment interval for carboplatin/cyclophosphamide courses when rescue was achieved with Taxol/cyclophosphamide-primed PBP was 17 days (range, 14 to 25). The median number of days to recovery of an absolute neutrophil count (ANC) greater than 0.5 was 8 (range, 5 to 12), and of self-sustaining platelet count greater than 20 × 109/L, 11 (range, 8 to 15). There was one episode of fatal sepsis. Of 13 patients assessable for response, there were five patients with pathologic complete responses (38.5%), six patients with microscopic residual disease (46%), and two patients with pathologic partial responses, for an overall response rate of 100%. Conclusion: The addition of escalating-dose Taxol to high-dose cyclophosphamide does not compromise PBP mobilization. The use of PBP mobilized in this fashion provides reliable engraftment after sequential administration of high-dose carboplatin/cyclophosphamide. Toxicities produced with this approach are manageable. The response rates demonstrated are promising and warrant further evaluation. © 1995 by American Society of Clinical Oncology.
Keywords: adult; clinical article; controlled study; treatment outcome; middle aged; clinical trial; advanced cancer; dose response; drug efficacy; paclitaxel; drug megadose; neoplasm staging; adenocarcinoma; ovarian neoplasms; carboplatin; controlled clinical trial; ovary cancer; antineoplastic combined chemotherapy protocols; drug administration schedule; tumor markers, biological; cyclophosphamide; antineoplastic activity; dose-response relationship, drug; stem cell; neutrophil; thrombocyte count; stem cells; leukocyte count; phase 1 clinical trial; antigens, cd; recombinant granulocyte colony stimulating factor; granulocyte colony-stimulating factor; antigens, cd34; cell motility; leukapheresis; humans; human; female; priority journal; article
Journal Title: Journal of Clinical Oncology
Volume: 13
Issue: 5
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 1995-05-01
Start Page: 1160
End Page: 1166
Language: English
DOI: 10.1200/jco.1995.13.5.1160
PUBMED: 7537799
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 28 August 2018 -- Source: Scopus
Altmetric Score
MSK Authors
  1. William Hoskins
    137 Hoskins
  2. Richard R Barakat
    588 Barakat
  3. Larry Norton
    563 Norton
  4. John P Curtin
    74 Curtin
  5. David R Spriggs
    312 Spriggs
  6. Lilian M Reich
    70 Reich
  7. Malcolm A S Moore
    420 Moore
  8. Thomas B Hakes
    11 Hakes