Fotemustine as second-line treatment for recurrent or progressive glioblastoma after concomitant and/or adjuvant temozolomide: a phase II trial of Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO)

Brandes, Alba A.; Tosoni, Alicia; Franceschi, Enrico; Blatt, V.; Santoro, Armando; Faedi, Marina; Amistà, Pietro; Gardiman, Marina Paola; Labianca, Roberto; Bianchini, Carlo; Ermani, Mario; Reni, Michele

doi:10.1007/s00280-009-0926-8

Cited by 90 publications

(55 citation statements)

References 25 publications

(29 reference statements)

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“…Progression-free survival at 6 months was 20.9%; three patients (7.1%) had partial response (PR) and 15 (34.9%) a disease stabilization (SD). The median survival was 6 months (95% CI 5-7) [7]. Interestingly, disease control rate was significantly greater in patients who started fotemustine at least 3 months after temozolamide administration had been concluded (76.9 vs. 26.7%, P = 0.002).…”

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confidence: 74%

“…However, this study enrolled also anaplastic tumors and the analysis of MMGT promoter was performed in less that 50% of cases. On the other hand, in the trial by Brandes et al the methylation status of MMGT was predictive of response (P = 0.044) [7]. Therefore, the exiguous number of samples analyzed needs a confirmation in a larger series particularly because the intra-tumoral methylation status may be a dynamic phenomenon dependent on the previous cytotoxic regimen the patient has received [11].…”

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confidence: 99%

“…On the other hand, on the side of cytotoxic drugs recent phase-II trials have demonstrated activity of nitrosoureas such as fotemustine in recurrent GBM [6][7][8][9]. Fotemustine is a third generation chloroethylnitrosourea containing a phosphoalanine carrier group grafted to the nitrosourea radical.…”

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confidence: 99%

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Fotemustine and recurrent glioblastoma: possible new opportunities for an old drug

Addeo

Santi²,

Prete

et al. 2009

Cancer Chemother Pharmacol

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confidence: 74%

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confidence: 99%

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Fotemustine and recurrent glioblastoma: possible new opportunities for an old drug

Addeo

Santi²,

Prete

et al. 2009

Cancer Chemother Pharmacol

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“…Fotemustine has been studied most extensively in that setting, with the 6-month pfs reported to be 20.9%-52% 104,107,108 . The combination of fotemustine-procarbazine may provide some benefit with respect to partial response and stable disease, but it does not appear to improve 6-month pfs 103 .…”

Section: 63mentioning

confidence: 99%

Canadian Recommendations for the Treatment of Recurrent or Progressive Glioblastoma Multiforme

Easaw¹,

Mason²,

Perry³

et al. 2011

Current Oncology

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Recommendation 1: Multidisciplinary Approach: To optimize treatment outcomes, the management of patients with recurrent glioblastoma should be individualized and should involve a multidisciplinary team approach, including neurosurgery, neuropathology, radiation oncology, neuro-oncology, and allied health professions. Recommendation 2: Imaging: The standard imaging modality for assessment of recurrent glioblastoma is Gd-enhanced magnetic resonance imaging (MRI). Tumour recurrence should be assessed according to the criteria set out by the Response Assessment in Neuro-Oncology Working Group. The optimal timing and frequency of MRI after chemoradiation and adjunctive therapy have not been established. Recommendation 3: Pseudo-progression: Progression observed by MRI after chemoradiation can be pseudo-progression. Accordingly, treated patients should not be classified as having progressive disease by Gd-enhancing MRI within the first 12 weeks after the end of radiotherapy unless new enhancement is observed outside the radiotherapy field or viable tumour is confirmed by pathology at the time of a required re-operation. Adjuvant temozolomide should be continued and follow-up imaging obtained. Recommendation 4: Repeat Surgery: Surgery can play a role in providing symptom relief and confirming tumour recurrence, pseudo-progression, or radiation necrosis. However, before surgical intervention, it is essential to clearly define treatment goals and the expected impact on prognosis and the patient’s quality of life. In the absence of level 1 evidence, the decision to re-operate should be made according to individual circumstances, in consultation with the multidisciplinary team and the patient. Recommendation 5: Re-irradiation: Re-irradiation is seldom recommended, but can be considered in carefully selected cases of recurrent glioblastoma. Recommendation 6: Systemic Therapy: Clinical trials, when available, should be offered to all eligible patients. In the absence of a trial, systemic therapy, including temozolomide rechallenge or antiangiogenic therapy, may be considered. Combination therapy is still experimental; optimal drug combinations and sequencing have not been established.

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“…The AVAREG trial [4] randomized 91 patients (2:1) to receive bevacizumab or fotemustine, a third generation nitrosourea, largely used in Italy [13]. RANO criteria were adopted for the disease assessment, and also Macdonald's criteria were recorded.…”

Section: Introductionmentioning

confidence: 99%

The role of bevacizumab in recurrent glioblastoma: new insights from randomized trials

Franceschi

Brandes

2015

CNS Oncol.

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The role of bevacizumab in the setting of recurrent glioblastoma (GBM) is still an argument of debate. In Europe, the EMA did not approve this agent despite the promising results in terms of response rate and progression-free survival provided by early Phase II studies without a calibration arm [1,2]. Therefore, new prospective randomized trials with bevacizumab in the recurrent setting have been conducted, and have been recently reported: the BELOB [3] and the AVAREG [4] trials.Both these trials adopted overall survival rates as primary end points, to avoid issues related to response assessment [5], and included a nitrosourea calibration arm, generating novel information in this setting.For many years response rate was considered the primary end point for Phase II studies in medical oncology. In neurooncology progression-free survival (PFS) and, in particular the incidence of patients free of progression at 6 months (PFS-6) have been considered the most appropriate end point for Phase II studies since the nineties [6], radiological responses being scarce (6-8%) [7,8], and there being a correlation between PFS and overall survival [9].Yet the action of bevacizumab on blood-brain barrier permeability directly affects the MRI evaluation made in these cases, thus potentially compromising the reliability of the assessment of the response rate and PFS. Therefore PFS-6 was no longer considered a sound end point [5].In the BELOB trial [3], a randomized Phase II study that enrolled 153 patients to receive bevacizumab alone or in combination with lomustine, or lomustine alone, Taal and Colleagues adopted the Response Assessment in Neuro-Oncology (RANO) criteria [10] for disease assessment, and reported that the radiological response following bevacizumab was correlated with survival (HR: 0.37; 95% CI: 0.23-0.58). These results are consistent with those reported in previous retrospective analyses in which imaging-based end points (response rate or PFS), obtained with bevacizumab were found to correlate with survival [11,12].Does this suggest that the best end point in Phase II studies should be re-reviewed?As yet, these findings are suggestive that neuroradiology still has a role in disease assessment for patients treated with bevacizumab, but further data are needed.

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Fotemustine as second-line treatment for recurrent or progressive glioblastoma after concomitant and/or adjuvant temozolomide: a phase II trial of Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO)

Cited by 90 publications

References 25 publications

Fotemustine and recurrent glioblastoma: possible new opportunities for an old drug

Fotemustine and recurrent glioblastoma: possible new opportunities for an old drug

Canadian Recommendations for the Treatment of Recurrent or Progressive Glioblastoma Multiforme

The role of bevacizumab in recurrent glioblastoma: new insights from randomized trials

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