Integration of filgrastim into chemoradiation for limited small cell lung cancer: A Phase I study

Bonnie Glisson, Ritsuko Komaki, Jin Soo Lee, Dong M. Shin, Frank Fossella, William K. Murphy, Jonathan Kurie, Roman Perez-Soler, Randi Schea, Saroj Vadhan-Raj

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Purpose: Recent studies document the value of early combined morality therapy of small cell lung cancer, but also indicate that early thoracic radiation adds to myelosuppression and can complicate further chemotherapy. Other studies indicate that simultaneous use of growth factors with thoracic radiation may be deleterious. However, temporal separation of growth factor use from cytotoxic therapy may allow dose intensity to be maintained/enhanced during combined modality treatment. We sought to integrate filgrastim into a novel chemoradiation regimen for patients with limited small cell lung cancer using an approach that separated growth factor administration from both chemotherapy and thoracic radiation. Methods and Materials: Twenty-seven patients with limited disease small cell lung cancer were enrolled in a Phase I trial of cisplatin, ifosfamide/mesna, oral etoposide, and thoracic radiation (1.5 Gy b.i.d. x 30 fractions days 1-19 cycle 1) ± filgrastim (5 μg/kg/day). Filgrastim was given on days 20-25 of cycle 1 after completion of radiation and following completion of oral etoposide in subsequent cycles. The primary end point was determination of maximum tolerated dose (MTD) of chemotherapy. Serial cohorts were treated with and without filgrastim. Results: Because of dose-limiting thrombocytopenia, primarily, and nonhematologic toxicity, the MTDs with and without filgrastim were identical (cisplatin 20 mg/m2 i.v. and ifosfamide 1200 mg/m2 i.v., both given days 1- 3, and etoposide 40 mg/m2 p.o. days 1-14). Filgrastim use shortened the duration of neutropenia at the MTD (median 4 vs. 7 days), but was not associated with a reduction in febrile neutropenia. Although growth factor administration did not allow dose escalation of this regimen, it did allow chemotherapy doses to be maintained at the MTD more frequently through four cycles of therapy. In the 24 evaluable patients, the overall response rate was 100% (71% partial and 29% complete). Conclusions: Despite careful attention to the timing of growth factor with chemoradiation, the administration of filgrastim with this regimen did not allow dose escalation. As in many other recent studies of hematopoietic growth factors given prophylactically with chemotherapy, the duration of neutropenia at the MTD was shortened and the need for dose reduction throughout treatment was reduced in patients receiving filgrastim at the MTD.

Original languageEnglish (US)
Pages (from-to)331-336
Number of pages6
JournalInternational Journal of Radiation Oncology Biology Physics
Volume40
Issue number2
DOIs
StatePublished - Jan 15 1998
Externally publishedYes

Fingerprint

Small Cell Lung Carcinoma
lungs
cancer
Maximum Tolerated Dose
dosage
Intercellular Signaling Peptides and Proteins
chemotherapy
Drug Therapy
Etoposide
Thorax
Radiation
Ifosfamide
Neutropenia
radiation
therapy
Cisplatin
cycles
Endpoint Determination
Mesna
Therapeutics

Keywords

  • Chemoradiation
  • Cisplatin
  • Hematopoietic growth factors
  • Ifosfamide
  • Oral etoposide
  • Small cell lung cancer

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

Integration of filgrastim into chemoradiation for limited small cell lung cancer : A Phase I study. / Glisson, Bonnie; Komaki, Ritsuko; Lee, Jin Soo; Shin, Dong M.; Fossella, Frank; Murphy, William K.; Kurie, Jonathan; Perez-Soler, Roman; Schea, Randi; Vadhan-Raj, Saroj.

In: International Journal of Radiation Oncology Biology Physics, Vol. 40, No. 2, 15.01.1998, p. 331-336.

Research output: Contribution to journalArticle

Glisson, Bonnie ; Komaki, Ritsuko ; Lee, Jin Soo ; Shin, Dong M. ; Fossella, Frank ; Murphy, William K. ; Kurie, Jonathan ; Perez-Soler, Roman ; Schea, Randi ; Vadhan-Raj, Saroj. / Integration of filgrastim into chemoradiation for limited small cell lung cancer : A Phase I study. In: International Journal of Radiation Oncology Biology Physics. 1998 ; Vol. 40, No. 2. pp. 331-336.
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abstract = "Purpose: Recent studies document the value of early combined morality therapy of small cell lung cancer, but also indicate that early thoracic radiation adds to myelosuppression and can complicate further chemotherapy. Other studies indicate that simultaneous use of growth factors with thoracic radiation may be deleterious. However, temporal separation of growth factor use from cytotoxic therapy may allow dose intensity to be maintained/enhanced during combined modality treatment. We sought to integrate filgrastim into a novel chemoradiation regimen for patients with limited small cell lung cancer using an approach that separated growth factor administration from both chemotherapy and thoracic radiation. Methods and Materials: Twenty-seven patients with limited disease small cell lung cancer were enrolled in a Phase I trial of cisplatin, ifosfamide/mesna, oral etoposide, and thoracic radiation (1.5 Gy b.i.d. x 30 fractions days 1-19 cycle 1) ± filgrastim (5 μg/kg/day). Filgrastim was given on days 20-25 of cycle 1 after completion of radiation and following completion of oral etoposide in subsequent cycles. The primary end point was determination of maximum tolerated dose (MTD) of chemotherapy. Serial cohorts were treated with and without filgrastim. Results: Because of dose-limiting thrombocytopenia, primarily, and nonhematologic toxicity, the MTDs with and without filgrastim were identical (cisplatin 20 mg/m2 i.v. and ifosfamide 1200 mg/m2 i.v., both given days 1- 3, and etoposide 40 mg/m2 p.o. days 1-14). Filgrastim use shortened the duration of neutropenia at the MTD (median 4 vs. 7 days), but was not associated with a reduction in febrile neutropenia. Although growth factor administration did not allow dose escalation of this regimen, it did allow chemotherapy doses to be maintained at the MTD more frequently through four cycles of therapy. In the 24 evaluable patients, the overall response rate was 100{\%} (71{\%} partial and 29{\%} complete). Conclusions: Despite careful attention to the timing of growth factor with chemoradiation, the administration of filgrastim with this regimen did not allow dose escalation. As in many other recent studies of hematopoietic growth factors given prophylactically with chemotherapy, the duration of neutropenia at the MTD was shortened and the need for dose reduction throughout treatment was reduced in patients receiving filgrastim at the MTD.",
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T2 - A Phase I study

AU - Glisson, Bonnie

AU - Komaki, Ritsuko

AU - Lee, Jin Soo

AU - Shin, Dong M.

AU - Fossella, Frank

AU - Murphy, William K.

AU - Kurie, Jonathan

AU - Perez-Soler, Roman

AU - Schea, Randi

AU - Vadhan-Raj, Saroj

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N2 - Purpose: Recent studies document the value of early combined morality therapy of small cell lung cancer, but also indicate that early thoracic radiation adds to myelosuppression and can complicate further chemotherapy. Other studies indicate that simultaneous use of growth factors with thoracic radiation may be deleterious. However, temporal separation of growth factor use from cytotoxic therapy may allow dose intensity to be maintained/enhanced during combined modality treatment. We sought to integrate filgrastim into a novel chemoradiation regimen for patients with limited small cell lung cancer using an approach that separated growth factor administration from both chemotherapy and thoracic radiation. Methods and Materials: Twenty-seven patients with limited disease small cell lung cancer were enrolled in a Phase I trial of cisplatin, ifosfamide/mesna, oral etoposide, and thoracic radiation (1.5 Gy b.i.d. x 30 fractions days 1-19 cycle 1) ± filgrastim (5 μg/kg/day). Filgrastim was given on days 20-25 of cycle 1 after completion of radiation and following completion of oral etoposide in subsequent cycles. The primary end point was determination of maximum tolerated dose (MTD) of chemotherapy. Serial cohorts were treated with and without filgrastim. Results: Because of dose-limiting thrombocytopenia, primarily, and nonhematologic toxicity, the MTDs with and without filgrastim were identical (cisplatin 20 mg/m2 i.v. and ifosfamide 1200 mg/m2 i.v., both given days 1- 3, and etoposide 40 mg/m2 p.o. days 1-14). Filgrastim use shortened the duration of neutropenia at the MTD (median 4 vs. 7 days), but was not associated with a reduction in febrile neutropenia. Although growth factor administration did not allow dose escalation of this regimen, it did allow chemotherapy doses to be maintained at the MTD more frequently through four cycles of therapy. In the 24 evaluable patients, the overall response rate was 100% (71% partial and 29% complete). Conclusions: Despite careful attention to the timing of growth factor with chemoradiation, the administration of filgrastim with this regimen did not allow dose escalation. As in many other recent studies of hematopoietic growth factors given prophylactically with chemotherapy, the duration of neutropenia at the MTD was shortened and the need for dose reduction throughout treatment was reduced in patients receiving filgrastim at the MTD.

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