Carboplatin/paclitaxel or carboplatin/vinorelbine followed by accelerated hyperfractionated conformal radiation therapy

Report of a prospective phase I dose escalation trial from the Carolina Conformal Therapy Consortium

Lawrence B. Marks, Jennifer Garst, Mark A. Socinski, Gregory Sibley, A. William Blackstock, James E. Herndon, Sumin Zhou, Timothy Shafman, Andrea Tisch, Robert Clough, Xiaoli Yu, Andrew Turrisi, Mitchell Anscher, Jeffrey Crawford, Julian Rosenman

Research output: Contribution to journalArticle

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Abstract

Purpose: To prospectively determine the maximum-tolerated dose of accelerated hyperfractionated conformal radiotherapy (RT; 1.6 Gy bid) for unresectable locally advanced lung cancer (IIB to IIIA/B) following induction carboplatin/paclitaxel (C/T) or carboplatin/vinorelbine (C/N). Methods: Induction chemotherapy, C/T or C/N, was followed by escalating doses of conformally-planned RT (73.6 to 86.4 Gy in 6.4-Gy increments). Concurrent boost methods delivered 1.6 and 1.25 Gy bid to the gross and clinical target volumes, respectively. Results: Between November 1997 and February 2002, 44 patients were enrolled (median age, 59 years; 59% male; stage III, 98%; median tumor size, 4 cm). Thirty-nine patients completed induction chemotherapy: 19 had a partial response, seven progressed, 15 had no response, and three were not assessable. Chemotherapy-associated toxicities were similar in the two chemotherapy groups. The incidence of grade ≥ 3 RT-induced toxicity was 1/13, 2/14, and 4/12 at 73.6, 80, and 86.4 Gy, respectively, thus defining the maximum tolerated dose at =80 Gy. Toxicities were in both lung and esophagus and were similar in the two chemotherapy arms. With a median followup of 34 months in the survivors, the actuarial 2-year survival was 47%, the median survival was 18 months. Fifteen patients had tumor relapse: 5 local failures in the high-dose volume, 2 regional failures outside of the high-dose volume, and 8 distant metastases. Conclusion: High-dose conformal twice-daily radiation therapy to approximately 80 Gy appears tolerable in well-selected patients with unresectable lung cancer following either C/T or C/N. Dose-limiting toxicities are mainly pulmonary and esophageal.

Original languageEnglish (US)
Pages (from-to)4329-4340
Number of pages12
JournalJournal of Clinical Oncology
Volume22
Issue number21
DOIs
StatePublished - Dec 1 2004

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Carboplatin
Paclitaxel
Radiotherapy
Induction Chemotherapy
Maximum Tolerated Dose
Drug Therapy
Lung Neoplasms
Conformal Radiotherapy
Therapeutics
Lung
Survival
Esophagus
Survivors
Neoplasms
vinorelbine
Neoplasm Metastasis
Recurrence
Incidence

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Carboplatin/paclitaxel or carboplatin/vinorelbine followed by accelerated hyperfractionated conformal radiation therapy : Report of a prospective phase I dose escalation trial from the Carolina Conformal Therapy Consortium. / Marks, Lawrence B.; Garst, Jennifer; Socinski, Mark A.; Sibley, Gregory; Blackstock, A. William; Herndon, James E.; Zhou, Sumin; Shafman, Timothy; Tisch, Andrea; Clough, Robert; Yu, Xiaoli; Turrisi, Andrew; Anscher, Mitchell; Crawford, Jeffrey; Rosenman, Julian.

In: Journal of Clinical Oncology, Vol. 22, No. 21, 01.12.2004, p. 4329-4340.

Research output: Contribution to journalArticle

Marks, LB, Garst, J, Socinski, MA, Sibley, G, Blackstock, AW, Herndon, JE, Zhou, S, Shafman, T, Tisch, A, Clough, R, Yu, X, Turrisi, A, Anscher, M, Crawford, J & Rosenman, J 2004, 'Carboplatin/paclitaxel or carboplatin/vinorelbine followed by accelerated hyperfractionated conformal radiation therapy: Report of a prospective phase I dose escalation trial from the Carolina Conformal Therapy Consortium', Journal of Clinical Oncology, vol. 22, no. 21, pp. 4329-4340. https://doi.org/10.1200/JCO.2004.02.165
Marks, Lawrence B. ; Garst, Jennifer ; Socinski, Mark A. ; Sibley, Gregory ; Blackstock, A. William ; Herndon, James E. ; Zhou, Sumin ; Shafman, Timothy ; Tisch, Andrea ; Clough, Robert ; Yu, Xiaoli ; Turrisi, Andrew ; Anscher, Mitchell ; Crawford, Jeffrey ; Rosenman, Julian. / Carboplatin/paclitaxel or carboplatin/vinorelbine followed by accelerated hyperfractionated conformal radiation therapy : Report of a prospective phase I dose escalation trial from the Carolina Conformal Therapy Consortium. In: Journal of Clinical Oncology. 2004 ; Vol. 22, No. 21. pp. 4329-4340.
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abstract = "Purpose: To prospectively determine the maximum-tolerated dose of accelerated hyperfractionated conformal radiotherapy (RT; 1.6 Gy bid) for unresectable locally advanced lung cancer (IIB to IIIA/B) following induction carboplatin/paclitaxel (C/T) or carboplatin/vinorelbine (C/N). Methods: Induction chemotherapy, C/T or C/N, was followed by escalating doses of conformally-planned RT (73.6 to 86.4 Gy in 6.4-Gy increments). Concurrent boost methods delivered 1.6 and 1.25 Gy bid to the gross and clinical target volumes, respectively. Results: Between November 1997 and February 2002, 44 patients were enrolled (median age, 59 years; 59{\%} male; stage III, 98{\%}; median tumor size, 4 cm). Thirty-nine patients completed induction chemotherapy: 19 had a partial response, seven progressed, 15 had no response, and three were not assessable. Chemotherapy-associated toxicities were similar in the two chemotherapy groups. The incidence of grade ≥ 3 RT-induced toxicity was 1/13, 2/14, and 4/12 at 73.6, 80, and 86.4 Gy, respectively, thus defining the maximum tolerated dose at =80 Gy. Toxicities were in both lung and esophagus and were similar in the two chemotherapy arms. With a median followup of 34 months in the survivors, the actuarial 2-year survival was 47{\%}, the median survival was 18 months. Fifteen patients had tumor relapse: 5 local failures in the high-dose volume, 2 regional failures outside of the high-dose volume, and 8 distant metastases. Conclusion: High-dose conformal twice-daily radiation therapy to approximately 80 Gy appears tolerable in well-selected patients with unresectable lung cancer following either C/T or C/N. Dose-limiting toxicities are mainly pulmonary and esophageal.",
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T1 - Carboplatin/paclitaxel or carboplatin/vinorelbine followed by accelerated hyperfractionated conformal radiation therapy

T2 - Report of a prospective phase I dose escalation trial from the Carolina Conformal Therapy Consortium

AU - Marks, Lawrence B.

AU - Garst, Jennifer

AU - Socinski, Mark A.

AU - Sibley, Gregory

AU - Blackstock, A. William

AU - Herndon, James E.

AU - Zhou, Sumin

AU - Shafman, Timothy

AU - Tisch, Andrea

AU - Clough, Robert

AU - Yu, Xiaoli

AU - Turrisi, Andrew

AU - Anscher, Mitchell

AU - Crawford, Jeffrey

AU - Rosenman, Julian

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N2 - Purpose: To prospectively determine the maximum-tolerated dose of accelerated hyperfractionated conformal radiotherapy (RT; 1.6 Gy bid) for unresectable locally advanced lung cancer (IIB to IIIA/B) following induction carboplatin/paclitaxel (C/T) or carboplatin/vinorelbine (C/N). Methods: Induction chemotherapy, C/T or C/N, was followed by escalating doses of conformally-planned RT (73.6 to 86.4 Gy in 6.4-Gy increments). Concurrent boost methods delivered 1.6 and 1.25 Gy bid to the gross and clinical target volumes, respectively. Results: Between November 1997 and February 2002, 44 patients were enrolled (median age, 59 years; 59% male; stage III, 98%; median tumor size, 4 cm). Thirty-nine patients completed induction chemotherapy: 19 had a partial response, seven progressed, 15 had no response, and three were not assessable. Chemotherapy-associated toxicities were similar in the two chemotherapy groups. The incidence of grade ≥ 3 RT-induced toxicity was 1/13, 2/14, and 4/12 at 73.6, 80, and 86.4 Gy, respectively, thus defining the maximum tolerated dose at =80 Gy. Toxicities were in both lung and esophagus and were similar in the two chemotherapy arms. With a median followup of 34 months in the survivors, the actuarial 2-year survival was 47%, the median survival was 18 months. Fifteen patients had tumor relapse: 5 local failures in the high-dose volume, 2 regional failures outside of the high-dose volume, and 8 distant metastases. Conclusion: High-dose conformal twice-daily radiation therapy to approximately 80 Gy appears tolerable in well-selected patients with unresectable lung cancer following either C/T or C/N. Dose-limiting toxicities are mainly pulmonary and esophageal.

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