An escalating dose finding study of liposomal doxorubicin and vinorelbine for the treatment of refractory or resistant epithelial ovarian cancer

R. Tambaro, S. Greggi, R. V. Iaffaioli, A. Rossi, C. Pisano, L. Manzione, E. Ferrari, M. Di Maio, F. Iodice, G. Casella, G. Laurelli, S. Pignata

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: The aim of this study was to determine the maximum tolerated dose (MTD) of liposomal doxorubicin (LD)-vinorelbine (V) in patients with refractory or resistant ovarian cancer. Patients and methods: Thirty patients were eligible. Seven levels were studied [LD 25-V20 (three patients enrolled); LD 30-V20 (three); LD 35-V20 (three); LD 20-V25 (three); LD 25-V25 (three); LD 30-V25 (10); LD 35-V25 (five)]. LD was given on day 1, while V was given on days 1 and 8 every 21 days. Cohorts of three patients were enrolled at each level, and another three patients were planned, if one dose-limiting toxicity (DLT) was registered. Results: DLT was observed in four patients: two febrile neutropenia, one grade 4 thrombocytopenia and one grade 3 palmar-plantar erythrodysesthesia (PPE) at level 7 (LD 35-V25). Thus, liposomal doxorubicin 30 mg/m2 plus vinorelbine 25 mg/m2 was the MTD. The most frequent toxicity was neutropenia. Fifteen patients (50%) experienced grade 3 neutropenia and 10 (33.3%) grade 4 neutropenia. Non-hematological toxicity was mild. Mucositis and PPE were the most frequent toxicities, but in most cases were grade 1. Out of 29 assessable patients, six (20.7%; 95% confidence interval 10%-39%) experienced an objective response, with one complete response. Conclusions: In patients with refractory or resistant ovarian cancer, the recommended doses for the combination studied are liposomal doxorubicin 30 mg/m2 (day 1) plus vinorelbine 25 mg/m2 (day 1 and 8). Neutropenia is the most frequent toxicity, while non-hematological toxicity is mild. Substantial activity was recorded and a phase II study is justified.

Original languageEnglish
Pages (from-to)1406-1411
Number of pages6
JournalAnnals of Oncology
Volume14
Issue number9
DOIs
Publication statusPublished - Sep 1 2003

Fingerprint

Neutropenia
Therapeutics
Maximum Tolerated Dose
Ovarian Neoplasms
liposomal doxorubicin
vinorelbine
Ovarian epithelial cancer
Febrile Neutropenia
Mucositis
Confidence Intervals

Keywords

  • Liposomal doxorubicin
  • Ovarian cancer
  • Phase I
  • Vinorelbine

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

An escalating dose finding study of liposomal doxorubicin and vinorelbine for the treatment of refractory or resistant epithelial ovarian cancer. / Tambaro, R.; Greggi, S.; Iaffaioli, R. V.; Rossi, A.; Pisano, C.; Manzione, L.; Ferrari, E.; Di Maio, M.; Iodice, F.; Casella, G.; Laurelli, G.; Pignata, S.

In: Annals of Oncology, Vol. 14, No. 9, 01.09.2003, p. 1406-1411.

Research output: Contribution to journalArticle

@article{f69e64a595fd45feb3fd15201c1fe596,
title = "An escalating dose finding study of liposomal doxorubicin and vinorelbine for the treatment of refractory or resistant epithelial ovarian cancer",
abstract = "Background: The aim of this study was to determine the maximum tolerated dose (MTD) of liposomal doxorubicin (LD)-vinorelbine (V) in patients with refractory or resistant ovarian cancer. Patients and methods: Thirty patients were eligible. Seven levels were studied [LD 25-V20 (three patients enrolled); LD 30-V20 (three); LD 35-V20 (three); LD 20-V25 (three); LD 25-V25 (three); LD 30-V25 (10); LD 35-V25 (five)]. LD was given on day 1, while V was given on days 1 and 8 every 21 days. Cohorts of three patients were enrolled at each level, and another three patients were planned, if one dose-limiting toxicity (DLT) was registered. Results: DLT was observed in four patients: two febrile neutropenia, one grade 4 thrombocytopenia and one grade 3 palmar-plantar erythrodysesthesia (PPE) at level 7 (LD 35-V25). Thus, liposomal doxorubicin 30 mg/m2 plus vinorelbine 25 mg/m2 was the MTD. The most frequent toxicity was neutropenia. Fifteen patients (50{\%}) experienced grade 3 neutropenia and 10 (33.3{\%}) grade 4 neutropenia. Non-hematological toxicity was mild. Mucositis and PPE were the most frequent toxicities, but in most cases were grade 1. Out of 29 assessable patients, six (20.7{\%}; 95{\%} confidence interval 10{\%}-39{\%}) experienced an objective response, with one complete response. Conclusions: In patients with refractory or resistant ovarian cancer, the recommended doses for the combination studied are liposomal doxorubicin 30 mg/m2 (day 1) plus vinorelbine 25 mg/m2 (day 1 and 8). Neutropenia is the most frequent toxicity, while non-hematological toxicity is mild. Substantial activity was recorded and a phase II study is justified.",
keywords = "Liposomal doxorubicin, Ovarian cancer, Phase I, Vinorelbine",
author = "R. Tambaro and S. Greggi and Iaffaioli, {R. V.} and A. Rossi and C. Pisano and L. Manzione and E. Ferrari and {Di Maio}, M. and F. Iodice and G. Casella and G. Laurelli and S. Pignata",
year = "2003",
month = "9",
day = "1",
doi = "10.1093/annonc/mdg364",
language = "English",
volume = "14",
pages = "1406--1411",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "NLM (Medline)",
number = "9",

}

TY - JOUR

T1 - An escalating dose finding study of liposomal doxorubicin and vinorelbine for the treatment of refractory or resistant epithelial ovarian cancer

AU - Tambaro, R.

AU - Greggi, S.

AU - Iaffaioli, R. V.

AU - Rossi, A.

AU - Pisano, C.

AU - Manzione, L.

AU - Ferrari, E.

AU - Di Maio, M.

AU - Iodice, F.

AU - Casella, G.

AU - Laurelli, G.

AU - Pignata, S.

PY - 2003/9/1

Y1 - 2003/9/1

N2 - Background: The aim of this study was to determine the maximum tolerated dose (MTD) of liposomal doxorubicin (LD)-vinorelbine (V) in patients with refractory or resistant ovarian cancer. Patients and methods: Thirty patients were eligible. Seven levels were studied [LD 25-V20 (three patients enrolled); LD 30-V20 (three); LD 35-V20 (three); LD 20-V25 (three); LD 25-V25 (three); LD 30-V25 (10); LD 35-V25 (five)]. LD was given on day 1, while V was given on days 1 and 8 every 21 days. Cohorts of three patients were enrolled at each level, and another three patients were planned, if one dose-limiting toxicity (DLT) was registered. Results: DLT was observed in four patients: two febrile neutropenia, one grade 4 thrombocytopenia and one grade 3 palmar-plantar erythrodysesthesia (PPE) at level 7 (LD 35-V25). Thus, liposomal doxorubicin 30 mg/m2 plus vinorelbine 25 mg/m2 was the MTD. The most frequent toxicity was neutropenia. Fifteen patients (50%) experienced grade 3 neutropenia and 10 (33.3%) grade 4 neutropenia. Non-hematological toxicity was mild. Mucositis and PPE were the most frequent toxicities, but in most cases were grade 1. Out of 29 assessable patients, six (20.7%; 95% confidence interval 10%-39%) experienced an objective response, with one complete response. Conclusions: In patients with refractory or resistant ovarian cancer, the recommended doses for the combination studied are liposomal doxorubicin 30 mg/m2 (day 1) plus vinorelbine 25 mg/m2 (day 1 and 8). Neutropenia is the most frequent toxicity, while non-hematological toxicity is mild. Substantial activity was recorded and a phase II study is justified.

AB - Background: The aim of this study was to determine the maximum tolerated dose (MTD) of liposomal doxorubicin (LD)-vinorelbine (V) in patients with refractory or resistant ovarian cancer. Patients and methods: Thirty patients were eligible. Seven levels were studied [LD 25-V20 (three patients enrolled); LD 30-V20 (three); LD 35-V20 (three); LD 20-V25 (three); LD 25-V25 (three); LD 30-V25 (10); LD 35-V25 (five)]. LD was given on day 1, while V was given on days 1 and 8 every 21 days. Cohorts of three patients were enrolled at each level, and another three patients were planned, if one dose-limiting toxicity (DLT) was registered. Results: DLT was observed in four patients: two febrile neutropenia, one grade 4 thrombocytopenia and one grade 3 palmar-plantar erythrodysesthesia (PPE) at level 7 (LD 35-V25). Thus, liposomal doxorubicin 30 mg/m2 plus vinorelbine 25 mg/m2 was the MTD. The most frequent toxicity was neutropenia. Fifteen patients (50%) experienced grade 3 neutropenia and 10 (33.3%) grade 4 neutropenia. Non-hematological toxicity was mild. Mucositis and PPE were the most frequent toxicities, but in most cases were grade 1. Out of 29 assessable patients, six (20.7%; 95% confidence interval 10%-39%) experienced an objective response, with one complete response. Conclusions: In patients with refractory or resistant ovarian cancer, the recommended doses for the combination studied are liposomal doxorubicin 30 mg/m2 (day 1) plus vinorelbine 25 mg/m2 (day 1 and 8). Neutropenia is the most frequent toxicity, while non-hematological toxicity is mild. Substantial activity was recorded and a phase II study is justified.

KW - Liposomal doxorubicin

KW - Ovarian cancer

KW - Phase I

KW - Vinorelbine

UR - http://www.scopus.com/inward/record.url?scp=17144438486&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=17144438486&partnerID=8YFLogxK

U2 - 10.1093/annonc/mdg364

DO - 10.1093/annonc/mdg364

M3 - Article

C2 - 12954580

AN - SCOPUS:17144438486

VL - 14

SP - 1406

EP - 1411

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 9

ER -