A phase I feasibility and pharmacokinetic study of intrapleural paclitaxel in patients with malignant pleural effusions

Reury Perng Perng, Ming Fang Wu, Shan Yang Lin, Yuh Min Chen, Jye Yee Lin, Jacqueline Whang-Peng

研究成果: 雜誌貢獻文章

20 引文 (Scopus)

摘要

To evaluate the feasibility and pharmacology of intrapleural (IP(L)) administration of paclitaxel, 18 patients with malignant pleural effusions were entered onto a phase I clinical study, 13 were caused by lung cancer. Following an effusion drainage rate of less than 100 ml/24 h and full expansion of the lung, patients were treated with a single instillation of paclitaxel administered IP(L) in 500 ml of normal saline and retained for a maximum of 96 h when tolerated. No systemic chemotherapy or ipsilateral thoracic irradiation was given for 4 weeks before and after the IP(L) treatment. The starting dose was 82.5 mg/m2 with the dose escalation schedule of 125, 175, 225 and 300 mg/m2. There were minimal local or systemic toxicities, such as local chest pain or myelosuppression, even when the paclitaxel dose reached 225 mg/m2. The pharmacological advantages of the IS administration of paclitaxel were demonstrated by the mean exposure of the pleural cavity (area under the concentration-time curve) to paclitaxel after IP(L) delivery exceeding that of the plasma by approximately 370-fold (range 55-684) and by the extraordinarily slow IP(L) clearance of paclitaxel (mean ± SE 0.49 ± 0.07 l/m2/day; range 0.08-1.16 l/ml/day) with significant concentrations of paclitaxel persisting within the cavity for more than 48-96 h after a single 19 instillation. In patients with detectable plasma paclitaxel levels, the plasma levels achieved exceed the minimal concentrations that are required to induce cytotoxic effects in vitro. Four patients had progressive dyspnea during IP(L) retention of paclitaxel solution because of treatment failure and needed drainage of effusion. One of these patients who was at the dose level of 225 mg/m2 originally had severely chronic obstructive lung disease, developed acute respiratory failure, refused mechanical ventilation support and succumbed to respiratory failure. No further patients were included after this event. Antitumor effect was shown by four of the 15 evaluable patients having no recurrence of effusion on chest radiograph at 1 month. Most of these responders had a good performance status, normal pretreatment pleural pH and/or glucose compared with the non-responders. We conclude that paclitaxel at a dose level of 175 or 225 mg/m2 is feasible for use intrapleurally. It could be considered for incorporation into treatment programs for patients with less advanced thoracic tumors with carcinomatous pleuritis or with 14 tumors following surgical debulking.
原文英語
頁(從 - 到)565-573
頁數9
期刊Anti-Cancer Drugs
8
發行號6
DOIs
出版狀態已發佈 - 九月 16 1997
對外發佈Yes

指紋

Malignant Pleural Effusion
Feasibility Studies
Paclitaxel
Pharmacokinetics
Thorax
Respiratory Insufficiency
Drainage
Pharmacology
Pleural Cavity
Neoplasms
Pleurisy
Treatment Failure
Chest Pain
Artificial Respiration
Dyspnea
Chronic Obstructive Pulmonary Disease
Lung Neoplasms
Appointments and Schedules

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Cancer Research

引用此文

A phase I feasibility and pharmacokinetic study of intrapleural paclitaxel in patients with malignant pleural effusions. / Perng, Reury Perng; Wu, Ming Fang; Lin, Shan Yang; Chen, Yuh Min; Lin, Jye Yee; Whang-Peng, Jacqueline.

於: Anti-Cancer Drugs, 卷 8, 編號 6, 16.09.1997, p. 565-573.

研究成果: 雜誌貢獻文章

Perng, Reury Perng ; Wu, Ming Fang ; Lin, Shan Yang ; Chen, Yuh Min ; Lin, Jye Yee ; Whang-Peng, Jacqueline. / A phase I feasibility and pharmacokinetic study of intrapleural paclitaxel in patients with malignant pleural effusions. 於: Anti-Cancer Drugs. 1997 ; 卷 8, 編號 6. 頁 565-573.
@article{1af3900357274b91932d2dc413c7bfc8,
title = "A phase I feasibility and pharmacokinetic study of intrapleural paclitaxel in patients with malignant pleural effusions",
abstract = "To evaluate the feasibility and pharmacology of intrapleural (IP(L)) administration of paclitaxel, 18 patients with malignant pleural effusions were entered onto a phase I clinical study, 13 were caused by lung cancer. Following an effusion drainage rate of less than 100 ml/24 h and full expansion of the lung, patients were treated with a single instillation of paclitaxel administered IP(L) in 500 ml of normal saline and retained for a maximum of 96 h when tolerated. No systemic chemotherapy or ipsilateral thoracic irradiation was given for 4 weeks before and after the IP(L) treatment. The starting dose was 82.5 mg/m2 with the dose escalation schedule of 125, 175, 225 and 300 mg/m2. There were minimal local or systemic toxicities, such as local chest pain or myelosuppression, even when the paclitaxel dose reached 225 mg/m2. The pharmacological advantages of the IS administration of paclitaxel were demonstrated by the mean exposure of the pleural cavity (area under the concentration-time curve) to paclitaxel after IP(L) delivery exceeding that of the plasma by approximately 370-fold (range 55-684) and by the extraordinarily slow IP(L) clearance of paclitaxel (mean ± SE 0.49 ± 0.07 l/m2/day; range 0.08-1.16 l/ml/day) with significant concentrations of paclitaxel persisting within the cavity for more than 48-96 h after a single 19 instillation. In patients with detectable plasma paclitaxel levels, the plasma levels achieved exceed the minimal concentrations that are required to induce cytotoxic effects in vitro. Four patients had progressive dyspnea during IP(L) retention of paclitaxel solution because of treatment failure and needed drainage of effusion. One of these patients who was at the dose level of 225 mg/m2 originally had severely chronic obstructive lung disease, developed acute respiratory failure, refused mechanical ventilation support and succumbed to respiratory failure. No further patients were included after this event. Antitumor effect was shown by four of the 15 evaluable patients having no recurrence of effusion on chest radiograph at 1 month. Most of these responders had a good performance status, normal pretreatment pleural pH and/or glucose compared with the non-responders. We conclude that paclitaxel at a dose level of 175 or 225 mg/m2 is feasible for use intrapleurally. It could be considered for incorporation into treatment programs for patients with less advanced thoracic tumors with carcinomatous pleuritis or with 14 tumors following surgical debulking.",
keywords = "Intrapleural paclitaxel, Malignant pleural effusions, Pharmacokinetics",
author = "Perng, {Reury Perng} and Wu, {Ming Fang} and Lin, {Shan Yang} and Chen, {Yuh Min} and Lin, {Jye Yee} and Jacqueline Whang-Peng",
year = "1997",
month = "9",
day = "16",
doi = "10.1097/00001813-199707000-00003",
language = "English",
volume = "8",
pages = "565--573",
journal = "Anti-Cancer Drugs",
issn = "0959-4973",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - A phase I feasibility and pharmacokinetic study of intrapleural paclitaxel in patients with malignant pleural effusions

AU - Perng, Reury Perng

AU - Wu, Ming Fang

AU - Lin, Shan Yang

AU - Chen, Yuh Min

AU - Lin, Jye Yee

AU - Whang-Peng, Jacqueline

PY - 1997/9/16

Y1 - 1997/9/16

N2 - To evaluate the feasibility and pharmacology of intrapleural (IP(L)) administration of paclitaxel, 18 patients with malignant pleural effusions were entered onto a phase I clinical study, 13 were caused by lung cancer. Following an effusion drainage rate of less than 100 ml/24 h and full expansion of the lung, patients were treated with a single instillation of paclitaxel administered IP(L) in 500 ml of normal saline and retained for a maximum of 96 h when tolerated. No systemic chemotherapy or ipsilateral thoracic irradiation was given for 4 weeks before and after the IP(L) treatment. The starting dose was 82.5 mg/m2 with the dose escalation schedule of 125, 175, 225 and 300 mg/m2. There were minimal local or systemic toxicities, such as local chest pain or myelosuppression, even when the paclitaxel dose reached 225 mg/m2. The pharmacological advantages of the IS administration of paclitaxel were demonstrated by the mean exposure of the pleural cavity (area under the concentration-time curve) to paclitaxel after IP(L) delivery exceeding that of the plasma by approximately 370-fold (range 55-684) and by the extraordinarily slow IP(L) clearance of paclitaxel (mean ± SE 0.49 ± 0.07 l/m2/day; range 0.08-1.16 l/ml/day) with significant concentrations of paclitaxel persisting within the cavity for more than 48-96 h after a single 19 instillation. In patients with detectable plasma paclitaxel levels, the plasma levels achieved exceed the minimal concentrations that are required to induce cytotoxic effects in vitro. Four patients had progressive dyspnea during IP(L) retention of paclitaxel solution because of treatment failure and needed drainage of effusion. One of these patients who was at the dose level of 225 mg/m2 originally had severely chronic obstructive lung disease, developed acute respiratory failure, refused mechanical ventilation support and succumbed to respiratory failure. No further patients were included after this event. Antitumor effect was shown by four of the 15 evaluable patients having no recurrence of effusion on chest radiograph at 1 month. Most of these responders had a good performance status, normal pretreatment pleural pH and/or glucose compared with the non-responders. We conclude that paclitaxel at a dose level of 175 or 225 mg/m2 is feasible for use intrapleurally. It could be considered for incorporation into treatment programs for patients with less advanced thoracic tumors with carcinomatous pleuritis or with 14 tumors following surgical debulking.

AB - To evaluate the feasibility and pharmacology of intrapleural (IP(L)) administration of paclitaxel, 18 patients with malignant pleural effusions were entered onto a phase I clinical study, 13 were caused by lung cancer. Following an effusion drainage rate of less than 100 ml/24 h and full expansion of the lung, patients were treated with a single instillation of paclitaxel administered IP(L) in 500 ml of normal saline and retained for a maximum of 96 h when tolerated. No systemic chemotherapy or ipsilateral thoracic irradiation was given for 4 weeks before and after the IP(L) treatment. The starting dose was 82.5 mg/m2 with the dose escalation schedule of 125, 175, 225 and 300 mg/m2. There were minimal local or systemic toxicities, such as local chest pain or myelosuppression, even when the paclitaxel dose reached 225 mg/m2. The pharmacological advantages of the IS administration of paclitaxel were demonstrated by the mean exposure of the pleural cavity (area under the concentration-time curve) to paclitaxel after IP(L) delivery exceeding that of the plasma by approximately 370-fold (range 55-684) and by the extraordinarily slow IP(L) clearance of paclitaxel (mean ± SE 0.49 ± 0.07 l/m2/day; range 0.08-1.16 l/ml/day) with significant concentrations of paclitaxel persisting within the cavity for more than 48-96 h after a single 19 instillation. In patients with detectable plasma paclitaxel levels, the plasma levels achieved exceed the minimal concentrations that are required to induce cytotoxic effects in vitro. Four patients had progressive dyspnea during IP(L) retention of paclitaxel solution because of treatment failure and needed drainage of effusion. One of these patients who was at the dose level of 225 mg/m2 originally had severely chronic obstructive lung disease, developed acute respiratory failure, refused mechanical ventilation support and succumbed to respiratory failure. No further patients were included after this event. Antitumor effect was shown by four of the 15 evaluable patients having no recurrence of effusion on chest radiograph at 1 month. Most of these responders had a good performance status, normal pretreatment pleural pH and/or glucose compared with the non-responders. We conclude that paclitaxel at a dose level of 175 or 225 mg/m2 is feasible for use intrapleurally. It could be considered for incorporation into treatment programs for patients with less advanced thoracic tumors with carcinomatous pleuritis or with 14 tumors following surgical debulking.

KW - Intrapleural paclitaxel

KW - Malignant pleural effusions

KW - Pharmacokinetics

UR - http://www.scopus.com/inward/record.url?scp=0030772757&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030772757&partnerID=8YFLogxK

U2 - 10.1097/00001813-199707000-00003

DO - 10.1097/00001813-199707000-00003

M3 - Article

C2 - 9300570

AN - SCOPUS:0030772757

VL - 8

SP - 565

EP - 573

JO - Anti-Cancer Drugs

JF - Anti-Cancer Drugs

SN - 0959-4973

IS - 6

ER -