Phase II Multicenter Trial with Carboplatin and Gemcitabine Induction Chemotherapy Followed by Radiotherapy Concomitantly with Low-Dose Paclitaxel and Gemcitabine for Stage IIIA and IIIB Non-small Cell Lung Cancer

Hirsh, Vera; Soulières, Denis; Duclos, Marie; Faria, Sergio; Vecchio, P. Del; Ofiara, Linda; Ayoub, Jean-Pierre; Charpentier, Danielle; Gruber, James; Portelance, Lorraine; Souhami, Luís

doi:10.1097/jto.0b013e3181560b92

Cited by 9 publications

(8 citation statements)

References 30 publications

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“…Therefore, we aimed not to radiosensitize with gemcitabine, 16 but applied the drug on Fridays after a weekly radiation course to cover the weekend radiation breaks, a schedule that has been carried out previously. 17 When administered in this way, the MTD of gemcitabine totaled 3300 mg/m 2 for a 6-week radiation/cisplatin course and exceeded previous reports (400, 18 900, 19 1200, 16 1500, 20 1800, 21 2250, 22 or 2400 23 mg/m 2 ).…”

Section: Discussionsupporting

confidence: 45%

Dose escalation of gemcitabine concomitant with radiation and cisplatin for nonsmall cell lung cancer

Momm

Kaden

Tannock

et al. 2010

Cancer

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BACKGROUND:The current study was conducted to evaluate the maximum tolerable dose of weekly gemcitabine administered simultaneously with radiation and cisplatin in patients with locally advanced nonsmall cell lung cancer (NSCLC). METHODS: Patients with stage IIIA/B NSCLC received concurrently 63 grays radiation and 20 mg/m 2 cisplatin Day 1 to 3 in Weeks 1 and 5, plus weekly gemcitabine at escalating doses (150-700 mg/m 2 ) on Fridays after radiation to avoid radiosensitization. The authors assessed dose-limiting toxicities according to Common Toxicity Criteria. The primary endpoint was maximum tolerated dose (MTD) of gemcitabine. Tumor resectability, survival, and disease-free survival (DFS) were also determined. RESULTS: Forty-two patients were accrued, of whom 95% received radiation and 66% cisplatin as above. Weekly doses of gemcitabine were escalated to 700 mg/m 2 . Grade 3 dysphagia and 1 case of fatal, probably treatment-related pulmonary deterioration established the MTD of gemcitabine at 550 mg/m 2 weekly. Twenty-five patients underwent surgery, and histopathological complete regression was documented in 26% of these patients. Overall, median actuarial survival and DFS were 23.8 and 12.4 months, respectively. CONCLUSIONS: Gemcitabine at doses up to 550 mg/m 2 weekly can be given simultaneously with radiation and cisplatin to patients with locally advanced NSCLC. Radical resection thereafter is feasible. The impact of this aggressive therapy should be evaluated further. Cancer 2010;116:4833-9.

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Section: Discussionsupporting

confidence: 45%

Dose escalation of gemcitabine concomitant with radiation and cisplatin for nonsmall cell lung cancer

Momm

Kaden

Tannock

et al. 2010

Cancer

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“…of 41 assessable patients who were treated with induction two cycles of carboplatin and gemcitabine 73.1% achieved PR and 24.4% SD. 20 Other publications from recent years showed lower PR and SD of 37% and 50% after two cycles of induction cisplatin and oral vinorelbine 21 , PR and SD of 36% and 52% after two cycles of induction gemcitabine and vinorelbine 22 , and PR and SD of 32.1% and 44.6% after two cycles of induction cisplatin and docetaxel. 23 …”

Section: Discussionmentioning

confidence: 91%

Induction Gemcitabine in Standard Dose or Prolonged Low-Dose with Cisplatin Followed By Concurrent Radiochemotherapy in Locally Advanced Non-Small Cell Lung Cancer: a Randomized Phase Ii Clinical Trial

2014

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Background The optimal combination of chemotherapy with radiation therapy for treatment locally advanced non-small cell lung cancer (NSCLC) remains an open issue. This randomized phase II study compared gemcitabine in two different schedules and cisplatin - as induction chemotherapy, followed by radiation therapy concurrent with cisplatin and etoposid. Patients and methods. Eligible patients had microscopically confirmed inoperable non-metastatic non-small cell lung cancer; fulfilled the standard criteria for platin-based chemotherapy; and signed informed consent. Patients were treated with 3 cycles of induction chemotherapy with gemcitabine and cisplatin. Two different aplications of gemcitabine were compared: patients in arm A received gemcitabine at 1250 mg/m 2 in a standard half hour i.v. infusion on days 1 and 8; patients in arm B received gemcitabine at 250 mg/m 2 in prolonged 6-hours i.v. infusion on days 1 and 8. In both arms, cisplatin 75 mg/m 2 on day 2 was administered. All patients continued treatment with radiation therapy with 60–66 Gy concurrent with cisplatin 50 mg/m 2 on days 1, 8, 29 and 36 and etoposid 50 mg/m 2 on days 1–5 and 29–33. The primary endpoint was response rate (RR) after induction chemotherapy; secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS). Results From September 2005 to November 2010, 106 patients were recruited to this study. No statistically signifficant differences were found in RR after induction chemotherapy between the two arms (48.1% and 57.4%, p = 0.34). Toxicity profile was comparable and mild with grade 3/4 neutropenia as primary toxicity in both arms. One patient in arm B suffered from acute peripheral ischemia grade 4 and an amputation of lower limb was needed. With a median follow-up of 69.3 months, progression-free survival and median survival in arm A were 15.7 and 24.8 months compared to 18.9 and 28.6 months in arm B. The figures for 1- and 3-year overall survival were 73.1% and 30.8% in arm A, and 81.5 % and 44.4% in arm B, respectively. Conclusions Among the two cisplatin-based doublets of induction chemotherapy for inoperable NSCLC, both schedules of gemcitabine have a comparable toxicity profile. Figures for RR, PFS and OS are among the best reported in current literature. While there is a trend towards better efficacy of the treament with prolonged infusion of gemcitabine, the difference between the two arms did not reach statistical significance.

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“…In the study by Hirsh et al . of 41 assessable patients who were treated with induction two cycles of carboplatin and gemcitabine 73.1% achieved PR and 24.4% SD 20. Other publications from recent years showed lower PR and SD of 37% and 50% after two cycles of induction cisplatin and oral vinorelbine21, PR and SD of 36% and 52% after two cycles of induction gemcitabine and vinorelbine22, and PR and SD of 32.1% and 44.6% after two cycles of induction cisplatin and docetaxel 23…”

Section: Discussionmentioning

confidence: 95%

Induction gemcitabine in standard dose or prolonged low-dose with cisplatin followed by concurrent radiochemotherapy in locally advanced non-small cell lung cancer: a randomized phase II clinical trial

Vrankar

Zwitter

Bavcar

et al. 2014

Radiology and Oncology

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Disclosure: No potential conflicts of interest were disclosed.Background. The optimal combination of chemotherapy with radiation therapy for treatment locally advanced non-small cell lung cancer (NSCLC) remains an open issue. This randomized phase II study compared gemcitabine in two different schedules and cisplatin -as induction chemotherapy, followed by radiation therapy concurrent with cisplatin and etoposid.Patients and methods. Eligible patients had microscopically confirmed inoperable non-metastatic non-small cell lung cancer; fulfilled the standard criteria for platin-based chemotherapy; and signed informed consent. Patients were treated with 3 cycles of induction chemotherapy with gemcitabine and cisplatin. Two different aplications of gemcitabine were compared: patients in arm A received gemcitabine at 1250 mg/m 2 in a standard half hour i.v. infusion on days 1 and 8; patients in arm B received gemcitabine at 250 mg/m 2 in prolonged 6-hours i.v. infusion on days 1 and 8. In both arms, cisplatin 75 mg/m 2 on day 2 was administered. All patients continued treatment with radiation therapy with 60-66 Gy concurrent with cisplatin 50 mg/m 2 on days 1, 8, 29 and 36 and etoposid 50 mg/m 2 on days 1-5 and 29-33. The primary endpoint was response rate (RR) after induction chemotherapy; secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS).Results. From September 2005 to November 2010, 106 patients were recruited to this study. No statistically signifficant differences were found in RR after induction chemotherapy between the two arms (48.1% and 57.4%, p = 0.34).Toxicity profile was comparable and mild with grade 3/4 neutropenia as primary toxicity in both arms. One patient in arm B suffered from acute peripheral ischemia grade 4 and an amputation of lower limb was needed. With a median follow-up of 69.3 months, progression-free survival and median survival in arm A were 15.7 and 24.8 months compared to 18.9 and 28.6 months in arm B. The figures for 1-and 3-year overall survival were 73.1% and 30.8% in arm A, and 81.5 % and 44.4% in arm B, respectively.Conclusions. Among the two cisplatin-based doublets of induction chemotherapy for inoperable NSCLC, both schedules of gemcitabine have a comparable toxicity profile. Figures for RR, PFS and OS are among the best reported in current literature. While there is a trend towards better efficacy of the treament with prolonged infusion of gemcitabine, the difference between the two arms did not reach statistical significance.

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Phase II Multicenter Trial with Carboplatin and Gemcitabine Induction Chemotherapy Followed by Radiotherapy Concomitantly with Low-Dose Paclitaxel and Gemcitabine for Stage IIIA and IIIB Non-small Cell Lung Cancer

Abstract: This regimen appears to be effective and was well tolerated. Further studies using this approach are warranted in patients with stage III NSCLC.

Cited by 9 publications

References 30 publications

Dose escalation of gemcitabine concomitant with radiation and cisplatin for nonsmall cell lung cancer

Dose escalation of gemcitabine concomitant with radiation and cisplatin for nonsmall cell lung cancer

Induction Gemcitabine in Standard Dose or Prolonged Low-Dose with Cisplatin Followed By Concurrent Radiochemotherapy in Locally Advanced Non-Small Cell Lung Cancer: a Randomized Phase Ii Clinical Trial

Induction gemcitabine in standard dose or prolonged low-dose with cisplatin followed by concurrent radiochemotherapy in locally advanced non-small cell lung cancer: a randomized phase II clinical trial

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