Results of a phase III study of early versus delayed whole brain radiotherapy with concurrent cisplatin and vinorelbine combination in inoperable brain metastasis of non-small-cell lung cancer: Groupe Français de Pneumo-Cancérologie (GFPC) Protocol 95-1

Robinet, G.; Thomas, P.; Breton, Jean-Luc; Léna, H.; Gouva, S.; Dabouis, G; Bennouna, Jaafar; Souquet, Pierre Jean; Balmès, P; Thiberville, Luc; Fournel, P.; Quoix, Élisabeth; Riou, R; Rebattu, P.; Pérol, Maurice; Paillotin, D.; Mornex, F.

doi:10.1023/a:1008338312647

Cited by 244 publications

(133 citation statements)

References 27 publications

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“…Although most of the studies pointed out an improvement in local control compared with WBRT, the median survival times did not differ (Postmus et al, 2000;Robinet et al, 2001;Ushio et al, 1991Mornex et al, 2003.…”

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confidence: 97%

A phase III trial of topotecan and whole brain radiation therapy for patients with CNS-metastases due to lung cancer

Neuhaus

Müller³

et al. 2009

Br J Cancer

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Brain metastases represent an important cause of morbidity in patients with lung cancer and are associated with a mean survival of less than 6 months. Thus, new regimens improving the outcome of these patients are urgently needed. On the basis of promising data raised in a phase I/II trial, we initiated an open, randomised, prospective, multicentric phase III trial, comparing whole brain radiation therapy (WBRT; 20 Â 2 Gy) alone with WBRT þ topotecan (RCT; 0.4 mg m À2 day À1 Â 20). A total of 320 patients with CNSmetastases due to SCLC or NSCLC were projected. The primary end point was overall survival, whereas second end points were local response and progression-free survival. However, until the cutoff date of study completion (i.e., a study duration of 34 months), only a total of 96 (RCT:47, WBRT:49) patients had been recruited, and so an analysis was performed at that time point. Although the numbers of grade 3/4 non-haematological toxicities (besides alopecia 115 (RCT/WBRT: 55 out of 60) were evenly distributed, the 25 haematological events occurred mainly in the combined treatment arm (24 out of 1). Local response, evaluated 2 weeks after treatment, was assessable in 44 (RCT/WBRT: 23 out of 21) patients, showing CR in eight (3 out of 5), PR in 17 (11 out of 6), SD in 14 (8 out of 6) and PD in five (1 out of 4) patients (all differences n.s.). Neither OAS (RCT/WBRT: median (days)): 87 out of 95, range 3 -752/4 -433; HR 1.32; 95% CI (0.83; 2.10)) nor PFS (median (days)): 71 out of 66, range, 3 -399/4 -228; HR 1.28, 95% CI (0.73; 2.43) differed significantly. On the basis of these results and the slow recruitment, a continuation of the study did not seem reasonable. The available data show no significant advantage for concurrent radiochemotherapy for patients with lung cancer; however, the recruited number of patients is too low to exhibit a small advantage of combined treatment.

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confidence: 97%

A phase III trial of topotecan and whole brain radiation therapy for patients with CNS-metastases due to lung cancer

Neuhaus

Müller³

et al. 2009

Br J Cancer

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“…The role of chemotherapy in patients with BrM by NSCLC is still controversial. However, among patients with NSCLC and BrM, response to different chemotherapy regimens, such cisplatin-gemcitabine or cisplatin-ifosfamide-irinotecan, was similar to that achieved in other disease sites [3][4][5][6][7][8][9]. Instead, for patients with recurrent or persistent BrM after WBRT and at least one line of chemotherapy, the treatment options available are limited.…”

Section: Discussionmentioning

confidence: 96%

“…Whole brain radiotherapy (WBRT) improves neurological symptoms in about 50% of patients and lengthens the median survival from 3 to 6 months [2]. Recent trials suggest that epipodophillotoxins alone or combined with cisplatin are very effective in treating NSCLCrelated BrM and ifosfamide-mitomycin-cisplatin or gemcitabine-cisplatin combinations have been evaluated with similar good responses [3][4][5][6][7][8][9]. Temozolomide (TMZ) is a novel, oral, alkylating agent with virtually 100% bioavailability [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Oral temozolomide in heavily pre-treated brain metastases from non-small cell lung cancer: Phase II study

Giorgio¹,

Giuffrida²,

Pappalardo³

et al. 2005

Lung Cancer

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Summary Introduction:The primary tumour type most likely to metastasize to the brain is lung cancer. In heavily pre-treated patients, limited therapeutic option is available and the results of availability therapies reported in literature are disappointing. The present phase II study was designed to assess the efficacy and safety of temozolomide (TMZ) as palliative treatment for brain metastases (BrM) in NSCLC patients pre-treated with WBRT and at least one line of chemotherapy for metastatic brain disease. Material and methods: Temozolomide was administered orally at 150 mg/mq/day for five consecutive days for the first cycle, doses were increased to 200 mg/mq/day for 5 days every 28 days for subsequent cycles if no grade 3/4 haematological toxicity was observed. Eligibility criteria included cytological or histological confirmed NSCLC; BrM, recurrent or progressing after WBRT and at least one line of chemotherapy. A total of 30 consecutive patients entered the study and received the allocated treatment.Results: Three patients (10%) achieved an objective response (OR) of BrM with two complete remission. Stable disease and progressive disease were achieved in 3 (10%) and 24 patients (80%), respectively. A correlation between response to TMZ * Corresponding author. and sensitivity to the previous first line chemotherapy was reported. Time to progression and overall survival were examined both for responder patients and for all included patients. For long-term survivors, we considered the patients who survived >12 months after the start of TMZ. According to this definition, three patients resulted long-term survivors: 2 with OR and 1 with stable brain disease. No grades 3 or 4 toxicity occurred. The total of treatment-related adverse events were mild or moderate (G1-2) in intensity. No patients discontinued TMZ as a result of treatment-related toxicity. Discussion: The results of the present trial clearly demonstrates that TMZ is active and safe in BrM NSCLC patients previously treated with WBRT and at least one line of chemotherapy.

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“…However, it is difficult for chemical agents to reach the intracranial lesions due to the presence of blood-brain barrier, which limits the application of chemotherapy for patients with BM. Many recent studies showed that the BBB is damaged in patients with BM (Robinet et al, 2001;Grimm, 2012). Damaged BBB allows many chemotherapy drugs to penetrate into the intracranial lesion, thus improving the efficacy of chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Whole Brain Radiotherapy Plus Chemotherapy in the Treatment of Brain Metastases from Lung Cancer: A Meta-analysis of 19 Randomized Controlled Trails

Liu¹,

Zeng²,

Qin³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Results of a phase III study of early versus delayed whole brain radiotherapy with concurrent cisplatin and vinorelbine combination in inoperable brain metastasis of non-small-cell lung cancer: Groupe Français de Pneumo-Cancérologie (GFPC) Protocol 95-1

Abstract: These results confirm the efficacy of chemotherapy in brain metastases of NSCLC and suggest that the timing (early or delayed) of WBRT did not influence survival of NSCLC with brain metastasis treated with concurrent chemotherapy.

Cited by 244 publications

References 27 publications

A phase III trial of topotecan and whole brain radiation therapy for patients with CNS-metastases due to lung cancer

A phase III trial of topotecan and whole brain radiation therapy for patients with CNS-metastases due to lung cancer

Oral temozolomide in heavily pre-treated brain metastases from non-small cell lung cancer: Phase II study

Whole Brain Radiotherapy Plus Chemotherapy in the Treatment of Brain Metastases from Lung Cancer: A Meta-analysis of 19 Randomized Controlled Trails

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