Phase I and pharmacologic study of 9-aminocamptothecin given by 72-hour infusion in adult cancer patients

W. Dahut, N. Harold, C. Takimoto, C. Allegra, A. Chen, J. M. Hamilton, S. Arbuck, M. Sorensen, F. Grollman, H. Nakashima, R. Lieberman, M. Liang, W. Corse, J. Grem

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Purpose: To conduct a phase I and pharmacologic study of the new topoisomerase I inhibitor, 9-aminocamptothecin (9-AC). Patients and Methods: A 72-hour infusion of 9-AC was administered every 14 days to 48 solid-tumor patients at doses of 5 to 59 μg/m2/h without granulocyte colony-stimulating factor (G-CSF) and 47 to 74 Hg/m2/h with G-CSF. Results: Without G-CSF, two of eight patients who received 47 μg/m2/h had dose-limiting neutropenia in their initial cycle, as did both patients who received 59 μg/m2/h (with a platelet count < 25,000/μL in one). With G-CSF, zero of seven patients treated with 47 μg/m2/h had dose-limiting neutropenia in their first cycle, while dose-limiting neutropenia occurred in six of 14 patients (with platelet count < 25,000/μL in five) entered at 59 μg/m2/h. Among 39 patients entered at ≥ 25 μg/m2/h 9-AC with or without G-CSF, fatigue, diarrhea, and nausea/vomiting of grade 2 severity ultimately occurred in 54%, 30%, and 38%, respectively, while grade 3 toxicity of each type occurred in 8% of patients. Steady-state 9-AC lactone concentration (Css) increased linearly from 0.89 to 10.6 nmol/L, and correlated strongly with leukopenia (r = .85). Conclusion: The recommended phase II dose of 9-AC given by our infusion every 2 weeks is 35 μg/m2/h without G-CSF or 47 μg/m2/h with G-CSF support. Dose escalation in individual patients may be possible according to their tolerance.

Original languageEnglish (US)
Pages (from-to)1236-1244
Number of pages9
JournalJournal of Clinical Oncology
Volume14
Issue number4
DOIs
StatePublished - Apr 1996

Fingerprint

9-aminocamptothecin
Granulocyte Colony-Stimulating Factor
Neoplasms
Neutropenia
Platelet Count
Topoisomerase I Inhibitors
Leukopenia

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Phase I and pharmacologic study of 9-aminocamptothecin given by 72-hour infusion in adult cancer patients. / Dahut, W.; Harold, N.; Takimoto, C.; Allegra, C.; Chen, A.; Hamilton, J. M.; Arbuck, S.; Sorensen, M.; Grollman, F.; Nakashima, H.; Lieberman, R.; Liang, M.; Corse, W.; Grem, J.

In: Journal of Clinical Oncology, Vol. 14, No. 4, 04.1996, p. 1236-1244.

Research output: Contribution to journalArticle

Dahut, W, Harold, N, Takimoto, C, Allegra, C, Chen, A, Hamilton, JM, Arbuck, S, Sorensen, M, Grollman, F, Nakashima, H, Lieberman, R, Liang, M, Corse, W & Grem, J 1996, 'Phase I and pharmacologic study of 9-aminocamptothecin given by 72-hour infusion in adult cancer patients', Journal of Clinical Oncology, vol. 14, no. 4, pp. 1236-1244. https://doi.org/10.1200/JCO.1996.14.4.1236
Dahut, W. ; Harold, N. ; Takimoto, C. ; Allegra, C. ; Chen, A. ; Hamilton, J. M. ; Arbuck, S. ; Sorensen, M. ; Grollman, F. ; Nakashima, H. ; Lieberman, R. ; Liang, M. ; Corse, W. ; Grem, J. / Phase I and pharmacologic study of 9-aminocamptothecin given by 72-hour infusion in adult cancer patients. In: Journal of Clinical Oncology. 1996 ; Vol. 14, No. 4. pp. 1236-1244.
@article{45b26b8a9d094b1883fc4aef6ed516c8,
title = "Phase I and pharmacologic study of 9-aminocamptothecin given by 72-hour infusion in adult cancer patients",
abstract = "Purpose: To conduct a phase I and pharmacologic study of the new topoisomerase I inhibitor, 9-aminocamptothecin (9-AC). Patients and Methods: A 72-hour infusion of 9-AC was administered every 14 days to 48 solid-tumor patients at doses of 5 to 59 μg/m2/h without granulocyte colony-stimulating factor (G-CSF) and 47 to 74 Hg/m2/h with G-CSF. Results: Without G-CSF, two of eight patients who received 47 μg/m2/h had dose-limiting neutropenia in their initial cycle, as did both patients who received 59 μg/m2/h (with a platelet count < 25,000/μL in one). With G-CSF, zero of seven patients treated with 47 μg/m2/h had dose-limiting neutropenia in their first cycle, while dose-limiting neutropenia occurred in six of 14 patients (with platelet count < 25,000/μL in five) entered at 59 μg/m2/h. Among 39 patients entered at ≥ 25 μg/m2/h 9-AC with or without G-CSF, fatigue, diarrhea, and nausea/vomiting of grade 2 severity ultimately occurred in 54{\%}, 30{\%}, and 38{\%}, respectively, while grade 3 toxicity of each type occurred in 8{\%} of patients. Steady-state 9-AC lactone concentration (Css) increased linearly from 0.89 to 10.6 nmol/L, and correlated strongly with leukopenia (r = .85). Conclusion: The recommended phase II dose of 9-AC given by our infusion every 2 weeks is 35 μg/m2/h without G-CSF or 47 μg/m2/h with G-CSF support. Dose escalation in individual patients may be possible according to their tolerance.",
author = "W. Dahut and N. Harold and C. Takimoto and C. Allegra and A. Chen and Hamilton, {J. M.} and S. Arbuck and M. Sorensen and F. Grollman and H. Nakashima and R. Lieberman and M. Liang and W. Corse and J. Grem",
year = "1996",
month = "4",
doi = "10.1200/JCO.1996.14.4.1236",
language = "English (US)",
volume = "14",
pages = "1236--1244",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "4",

}

TY - JOUR

T1 - Phase I and pharmacologic study of 9-aminocamptothecin given by 72-hour infusion in adult cancer patients

AU - Dahut, W.

AU - Harold, N.

AU - Takimoto, C.

AU - Allegra, C.

AU - Chen, A.

AU - Hamilton, J. M.

AU - Arbuck, S.

AU - Sorensen, M.

AU - Grollman, F.

AU - Nakashima, H.

AU - Lieberman, R.

AU - Liang, M.

AU - Corse, W.

AU - Grem, J.

PY - 1996/4

Y1 - 1996/4

N2 - Purpose: To conduct a phase I and pharmacologic study of the new topoisomerase I inhibitor, 9-aminocamptothecin (9-AC). Patients and Methods: A 72-hour infusion of 9-AC was administered every 14 days to 48 solid-tumor patients at doses of 5 to 59 μg/m2/h without granulocyte colony-stimulating factor (G-CSF) and 47 to 74 Hg/m2/h with G-CSF. Results: Without G-CSF, two of eight patients who received 47 μg/m2/h had dose-limiting neutropenia in their initial cycle, as did both patients who received 59 μg/m2/h (with a platelet count < 25,000/μL in one). With G-CSF, zero of seven patients treated with 47 μg/m2/h had dose-limiting neutropenia in their first cycle, while dose-limiting neutropenia occurred in six of 14 patients (with platelet count < 25,000/μL in five) entered at 59 μg/m2/h. Among 39 patients entered at ≥ 25 μg/m2/h 9-AC with or without G-CSF, fatigue, diarrhea, and nausea/vomiting of grade 2 severity ultimately occurred in 54%, 30%, and 38%, respectively, while grade 3 toxicity of each type occurred in 8% of patients. Steady-state 9-AC lactone concentration (Css) increased linearly from 0.89 to 10.6 nmol/L, and correlated strongly with leukopenia (r = .85). Conclusion: The recommended phase II dose of 9-AC given by our infusion every 2 weeks is 35 μg/m2/h without G-CSF or 47 μg/m2/h with G-CSF support. Dose escalation in individual patients may be possible according to their tolerance.

AB - Purpose: To conduct a phase I and pharmacologic study of the new topoisomerase I inhibitor, 9-aminocamptothecin (9-AC). Patients and Methods: A 72-hour infusion of 9-AC was administered every 14 days to 48 solid-tumor patients at doses of 5 to 59 μg/m2/h without granulocyte colony-stimulating factor (G-CSF) and 47 to 74 Hg/m2/h with G-CSF. Results: Without G-CSF, two of eight patients who received 47 μg/m2/h had dose-limiting neutropenia in their initial cycle, as did both patients who received 59 μg/m2/h (with a platelet count < 25,000/μL in one). With G-CSF, zero of seven patients treated with 47 μg/m2/h had dose-limiting neutropenia in their first cycle, while dose-limiting neutropenia occurred in six of 14 patients (with platelet count < 25,000/μL in five) entered at 59 μg/m2/h. Among 39 patients entered at ≥ 25 μg/m2/h 9-AC with or without G-CSF, fatigue, diarrhea, and nausea/vomiting of grade 2 severity ultimately occurred in 54%, 30%, and 38%, respectively, while grade 3 toxicity of each type occurred in 8% of patients. Steady-state 9-AC lactone concentration (Css) increased linearly from 0.89 to 10.6 nmol/L, and correlated strongly with leukopenia (r = .85). Conclusion: The recommended phase II dose of 9-AC given by our infusion every 2 weeks is 35 μg/m2/h without G-CSF or 47 μg/m2/h with G-CSF support. Dose escalation in individual patients may be possible according to their tolerance.

UR - http://www.scopus.com/inward/record.url?scp=9244231199&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=9244231199&partnerID=8YFLogxK

U2 - 10.1200/JCO.1996.14.4.1236

DO - 10.1200/JCO.1996.14.4.1236

M3 - Article

C2 - 8648379

AN - SCOPUS:9244231199

VL - 14

SP - 1236

EP - 1244

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 4

ER -