Phase I study of paclitaxel administered by ten-day continuous infusion

Ronald J. Shade, Katherine M W Pisters, Martin H. Huber, Frank Fossella, Roman Perez-Soler, Dong M. Shin, Jonathan Kurie, Bonnie Glisson, Scott Lippman, Jin Soo Lee

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Purpose: Pre-clinical data have suggested that prolonged exposure to paclitaxel enhances its cytotoxicity, but various clinical trials utilizing long-term infusions of paclitaxel have been limited by unacceptable hematologic toxicity, most notably significant neutropenia. A phase I study of paclitaxel administered over 10 days, was performed to evaluate the hematologic and non-hematologic toxicities as well as to determine the maximum-tolerated dose for the 10-day infusion duration. Patients and methods: Twenty-nine solid tumor patients (predominantly non-small cell lung cancer and head and neck cancer) were treated with paclitaxel at doses ranging from 5 mg/m2/day to 25 mg/m2/day administered as a 10-day continuous infusion via a pump every 21 days. Dose escalation was permitted within individual patients. Dose-limiting toxicity (DLT) was defined as grade 3 or 4 non-hematologic toxicity, ANC ≤ 500 or platelet count ≤ 25,000 for ≥ 7 days or febrile neutropenia. The maximum tolerated dose (MTD) was defined as the highest dose level at which less than two out of six patients developed DLT. All of the patients had received prior chemotherapy; approximately two-thirds had received prior radiation as well. All patients received standard pre-medications for paclitaxel, including anti-histamines and corticosteroids. Prophylactic granulocyte colony-stimulating factor (GCSF) was not used. Results: A total of 110 courses of paclitaxel were administered to 29 patients. The incidence of hematologic and non-hematologic toxicity was quite low among the patients treated at dose levels below 17 mg/m2/day. At higher doses, non-hematologic toxicities including arthralgias, myalgias, fatigue, nausea, stomatitis, and peripheral neuropathy were seen, although nearly all of the toxicities were less than grade 3 (NCl toxicity criteria). Hematologic toxicity mostly consisted of neutropenia and was more common at dose levels of 17 mg/m2/day or higher. Nevertheless, even at the highest dose levels (21 mg/m2/day and 25 mg/m2/day) grade 3 or 4 neutropenia occurred in only 50% of patients. Dose-limiting hematologic toxicity occurred in 2 of 4 patients treated at the 25 mg/m2/day dose level. Conclusion: Paclitaxel can be safely administered as a 10-day infusion. The MTD for this schedule is 210 mg/m2. Unlike the 96-hour paclitaxel infusions, dose-reduction for myelosuppression may not be necessary because the MTD of paclitaxel when administered over a 10-day infusion is similar to the MTD of paclitaxel when infused over 3 or 24 hours.

Original languageEnglish (US)
Pages (from-to)237-243
Number of pages7
JournalInvestigational New Drugs
Volume16
Issue number3
DOIs
StatePublished - 1998
Externally publishedYes

Fingerprint

Paclitaxel
Maximum Tolerated Dose
Neutropenia
Head and Neck Neoplasms
Febrile Neutropenia
Stomatitis
Myalgia
Arthralgia
Peripheral Nervous System Diseases
Granulocyte Colony-Stimulating Factor
Platelet Count
Non-Small Cell Lung Carcinoma
Nausea
Histamine
Fatigue
Appointments and Schedules
Adrenal Cortex Hormones
Clinical Trials
Radiation
Drug Therapy

Keywords

  • Chemotherapy
  • Continuous infusion
  • Myelosuppression
  • Paclitaxel

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Shade, R. J., Pisters, K. M. W., Huber, M. H., Fossella, F., Perez-Soler, R., Shin, D. M., ... Lee, J. S. (1998). Phase I study of paclitaxel administered by ten-day continuous infusion. Investigational New Drugs, 16(3), 237-243. https://doi.org/10.1023/A:1006157226693

Phase I study of paclitaxel administered by ten-day continuous infusion. / Shade, Ronald J.; Pisters, Katherine M W; Huber, Martin H.; Fossella, Frank; Perez-Soler, Roman; Shin, Dong M.; Kurie, Jonathan; Glisson, Bonnie; Lippman, Scott; Lee, Jin Soo.

In: Investigational New Drugs, Vol. 16, No. 3, 1998, p. 237-243.

Research output: Contribution to journalArticle

Shade, RJ, Pisters, KMW, Huber, MH, Fossella, F, Perez-Soler, R, Shin, DM, Kurie, J, Glisson, B, Lippman, S & Lee, JS 1998, 'Phase I study of paclitaxel administered by ten-day continuous infusion', Investigational New Drugs, vol. 16, no. 3, pp. 237-243. https://doi.org/10.1023/A:1006157226693
Shade, Ronald J. ; Pisters, Katherine M W ; Huber, Martin H. ; Fossella, Frank ; Perez-Soler, Roman ; Shin, Dong M. ; Kurie, Jonathan ; Glisson, Bonnie ; Lippman, Scott ; Lee, Jin Soo. / Phase I study of paclitaxel administered by ten-day continuous infusion. In: Investigational New Drugs. 1998 ; Vol. 16, No. 3. pp. 237-243.
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