Phase I study of dose-dense alternating doublets in advanced non-small-cell lung cancer

Everett E. Vokes, Chaiyut Charoentum, Gary S. Gordon, Charles M. Rudin, Stuart A. Krauss, Philip C. Hoffman, Ann M. Mauer, Susie Lee, Sylvia Watson

Research output: Contribution to journalArticle

Abstract

We performed a study to determine the feasibility of a rapidly alternating administration of cisplatin/vinorelbine (CV) and docetaxel/gemcitabine (DG) in the treatment of advanced non-small-cell lung cancer (NSCLC). Thirty-four patients with NSCLC (6% stage IIIB, 94% stage IV) were enrolled. The initial schema was to give CV on days 1 and 8 followed by DG on days 15 and 22, every 28 days. Granulocyte colony-stimulating factor (G-CSF) was used on days 9-14 and 23-28. Despite dose reductions, this sequence was not feasible. Therefore, the sequence was switched to give DG before CV, cycle duration was extended to 35 days, and G-CSF was given on days 2-7 and 23-28. Neutropenia and thrombocytopenia were dose-limiting toxicities. The recommended doses for phase II studies are docetaxel 75 mg/m2 on day 1, gemcitabine 1000 mg/m2 on days 1 and 8, cisplatin 60 mg/m2 on day 15, and vinorelbine 25 mg/m2 on days 15 and 22, every 35 days with G-CSF 5 μg/kg on days 2-7 and 23-28. However, treatment delays were required in subsequent cycles due to cumulative myelosuppression. A less intensive schedule is recommended for subsequent cycles for further testing. Overall response rate was 29% (95% confidence interval [CI], 14%-45%), and median survival for all patients was 11.8 months. One- and 2-year survival rates were 47% (95% CI, 30%-63%) and 14% (95% CI, 1.4%-40%), respectively. Although initial administration of this regimen was feasible, dose intensity could not be maintained in subsequent cycles due to cumulative myelosuppression. A sequential rather than alternating use of doublet regimens might be more readily feasible and may permit greater maintenance of dose intensity.

Original languageEnglish (US)
Pages (from-to)265-270
Number of pages6
JournalClinical Lung Cancer
Volume3
Issue number4
StatePublished - 2002
Externally publishedYes

Fingerprint

docetaxel
gemcitabine
Non-Small Cell Lung Carcinoma
Cisplatin
Granulocyte Colony-Stimulating Factor
Confidence Intervals
Neutropenia
Thrombocytopenia
Appointments and Schedules
Survival Rate
Maintenance
Survival
vinorelbine
Therapeutics

Keywords

  • Alternating chemotherapy
  • Cisplatin
  • Docetaxel
  • Dose-dense chemotherapy
  • Gemcitabine
  • Vinorelbine

ASJC Scopus subject areas

  • Cancer Research
  • Pulmonary and Respiratory Medicine

Cite this

Vokes, E. E., Charoentum, C., Gordon, G. S., Rudin, C. M., Krauss, S. A., Hoffman, P. C., ... Watson, S. (2002). Phase I study of dose-dense alternating doublets in advanced non-small-cell lung cancer. Clinical Lung Cancer, 3(4), 265-270.

Phase I study of dose-dense alternating doublets in advanced non-small-cell lung cancer. / Vokes, Everett E.; Charoentum, Chaiyut; Gordon, Gary S.; Rudin, Charles M.; Krauss, Stuart A.; Hoffman, Philip C.; Mauer, Ann M.; Lee, Susie; Watson, Sylvia.

In: Clinical Lung Cancer, Vol. 3, No. 4, 2002, p. 265-270.

Research output: Contribution to journalArticle

Vokes, EE, Charoentum, C, Gordon, GS, Rudin, CM, Krauss, SA, Hoffman, PC, Mauer, AM, Lee, S & Watson, S 2002, 'Phase I study of dose-dense alternating doublets in advanced non-small-cell lung cancer', Clinical Lung Cancer, vol. 3, no. 4, pp. 265-270.
Vokes EE, Charoentum C, Gordon GS, Rudin CM, Krauss SA, Hoffman PC et al. Phase I study of dose-dense alternating doublets in advanced non-small-cell lung cancer. Clinical Lung Cancer. 2002;3(4):265-270.
Vokes, Everett E. ; Charoentum, Chaiyut ; Gordon, Gary S. ; Rudin, Charles M. ; Krauss, Stuart A. ; Hoffman, Philip C. ; Mauer, Ann M. ; Lee, Susie ; Watson, Sylvia. / Phase I study of dose-dense alternating doublets in advanced non-small-cell lung cancer. In: Clinical Lung Cancer. 2002 ; Vol. 3, No. 4. pp. 265-270.
@article{990851d6e22444b6b2eafa8461d5a1a2,
title = "Phase I study of dose-dense alternating doublets in advanced non-small-cell lung cancer",
abstract = "We performed a study to determine the feasibility of a rapidly alternating administration of cisplatin/vinorelbine (CV) and docetaxel/gemcitabine (DG) in the treatment of advanced non-small-cell lung cancer (NSCLC). Thirty-four patients with NSCLC (6{\%} stage IIIB, 94{\%} stage IV) were enrolled. The initial schema was to give CV on days 1 and 8 followed by DG on days 15 and 22, every 28 days. Granulocyte colony-stimulating factor (G-CSF) was used on days 9-14 and 23-28. Despite dose reductions, this sequence was not feasible. Therefore, the sequence was switched to give DG before CV, cycle duration was extended to 35 days, and G-CSF was given on days 2-7 and 23-28. Neutropenia and thrombocytopenia were dose-limiting toxicities. The recommended doses for phase II studies are docetaxel 75 mg/m2 on day 1, gemcitabine 1000 mg/m2 on days 1 and 8, cisplatin 60 mg/m2 on day 15, and vinorelbine 25 mg/m2 on days 15 and 22, every 35 days with G-CSF 5 μg/kg on days 2-7 and 23-28. However, treatment delays were required in subsequent cycles due to cumulative myelosuppression. A less intensive schedule is recommended for subsequent cycles for further testing. Overall response rate was 29{\%} (95{\%} confidence interval [CI], 14{\%}-45{\%}), and median survival for all patients was 11.8 months. One- and 2-year survival rates were 47{\%} (95{\%} CI, 30{\%}-63{\%}) and 14{\%} (95{\%} CI, 1.4{\%}-40{\%}), respectively. Although initial administration of this regimen was feasible, dose intensity could not be maintained in subsequent cycles due to cumulative myelosuppression. A sequential rather than alternating use of doublet regimens might be more readily feasible and may permit greater maintenance of dose intensity.",
keywords = "Alternating chemotherapy, Cisplatin, Docetaxel, Dose-dense chemotherapy, Gemcitabine, Vinorelbine",
author = "Vokes, {Everett E.} and Chaiyut Charoentum and Gordon, {Gary S.} and Rudin, {Charles M.} and Krauss, {Stuart A.} and Hoffman, {Philip C.} and Mauer, {Ann M.} and Susie Lee and Sylvia Watson",
year = "2002",
language = "English (US)",
volume = "3",
pages = "265--270",
journal = "Clinical Lung Cancer",
issn = "1525-7304",
publisher = "Elsevier",
number = "4",

}

TY - JOUR

T1 - Phase I study of dose-dense alternating doublets in advanced non-small-cell lung cancer

AU - Vokes, Everett E.

AU - Charoentum, Chaiyut

AU - Gordon, Gary S.

AU - Rudin, Charles M.

AU - Krauss, Stuart A.

AU - Hoffman, Philip C.

AU - Mauer, Ann M.

AU - Lee, Susie

AU - Watson, Sylvia

PY - 2002

Y1 - 2002

N2 - We performed a study to determine the feasibility of a rapidly alternating administration of cisplatin/vinorelbine (CV) and docetaxel/gemcitabine (DG) in the treatment of advanced non-small-cell lung cancer (NSCLC). Thirty-four patients with NSCLC (6% stage IIIB, 94% stage IV) were enrolled. The initial schema was to give CV on days 1 and 8 followed by DG on days 15 and 22, every 28 days. Granulocyte colony-stimulating factor (G-CSF) was used on days 9-14 and 23-28. Despite dose reductions, this sequence was not feasible. Therefore, the sequence was switched to give DG before CV, cycle duration was extended to 35 days, and G-CSF was given on days 2-7 and 23-28. Neutropenia and thrombocytopenia were dose-limiting toxicities. The recommended doses for phase II studies are docetaxel 75 mg/m2 on day 1, gemcitabine 1000 mg/m2 on days 1 and 8, cisplatin 60 mg/m2 on day 15, and vinorelbine 25 mg/m2 on days 15 and 22, every 35 days with G-CSF 5 μg/kg on days 2-7 and 23-28. However, treatment delays were required in subsequent cycles due to cumulative myelosuppression. A less intensive schedule is recommended for subsequent cycles for further testing. Overall response rate was 29% (95% confidence interval [CI], 14%-45%), and median survival for all patients was 11.8 months. One- and 2-year survival rates were 47% (95% CI, 30%-63%) and 14% (95% CI, 1.4%-40%), respectively. Although initial administration of this regimen was feasible, dose intensity could not be maintained in subsequent cycles due to cumulative myelosuppression. A sequential rather than alternating use of doublet regimens might be more readily feasible and may permit greater maintenance of dose intensity.

AB - We performed a study to determine the feasibility of a rapidly alternating administration of cisplatin/vinorelbine (CV) and docetaxel/gemcitabine (DG) in the treatment of advanced non-small-cell lung cancer (NSCLC). Thirty-four patients with NSCLC (6% stage IIIB, 94% stage IV) were enrolled. The initial schema was to give CV on days 1 and 8 followed by DG on days 15 and 22, every 28 days. Granulocyte colony-stimulating factor (G-CSF) was used on days 9-14 and 23-28. Despite dose reductions, this sequence was not feasible. Therefore, the sequence was switched to give DG before CV, cycle duration was extended to 35 days, and G-CSF was given on days 2-7 and 23-28. Neutropenia and thrombocytopenia were dose-limiting toxicities. The recommended doses for phase II studies are docetaxel 75 mg/m2 on day 1, gemcitabine 1000 mg/m2 on days 1 and 8, cisplatin 60 mg/m2 on day 15, and vinorelbine 25 mg/m2 on days 15 and 22, every 35 days with G-CSF 5 μg/kg on days 2-7 and 23-28. However, treatment delays were required in subsequent cycles due to cumulative myelosuppression. A less intensive schedule is recommended for subsequent cycles for further testing. Overall response rate was 29% (95% confidence interval [CI], 14%-45%), and median survival for all patients was 11.8 months. One- and 2-year survival rates were 47% (95% CI, 30%-63%) and 14% (95% CI, 1.4%-40%), respectively. Although initial administration of this regimen was feasible, dose intensity could not be maintained in subsequent cycles due to cumulative myelosuppression. A sequential rather than alternating use of doublet regimens might be more readily feasible and may permit greater maintenance of dose intensity.

KW - Alternating chemotherapy

KW - Cisplatin

KW - Docetaxel

KW - Dose-dense chemotherapy

KW - Gemcitabine

KW - Vinorelbine

UR - http://www.scopus.com/inward/record.url?scp=0036308914&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036308914&partnerID=8YFLogxK

M3 - Article

C2 - 14662035

AN - SCOPUS:0036308914

VL - 3

SP - 265

EP - 270

JO - Clinical Lung Cancer

JF - Clinical Lung Cancer

SN - 1525-7304

IS - 4

ER -