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Paclitaxel for metastatic germ-cell tumour
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Reducing radiation to the brain
CC Studio/Science Photo Library
Adjuvant stereotactic radiotherapy of the resection cavity for brain metastases compares favourably with postoperative whole-brain irradiation (Int J Radiat Oncol Biol Phys 2008; 70: 187–93). In a retrospective analysis, Scott Soltys and colleagues (Stanford University Medical Center, CA, USA)
Stereotactic radiotherapy of the brain might control local recurrence
identified 72 patients with brain metastases who had been given stereotactic radiotherapy of the resection cavity. Whole-brain irradiation was deferred in each case until local tumour recurrence. Patients received a median marginal dose of 18·0 Gy (range 15·0–30·0), and had a follow-up MRI at 3 months to assess local control. Seven patients died before follow-up; however, all 72 patients were included in the survival analysis. Local control at 6 months and 12 months was 88% and 79%, respectively. For the ten patients who had recurrence, median time-toprogression was 5·7 months (range 3·2–14·2). Median overall survival for all 72 patients was 15·1 months (range 0·8–80·5). Overall survival at 6 months and 12 months was 77% and 57%, respectively. Seven patients had symptomatic post-treatment oedema, three of which
had surgical resection of a region of necrosis to decrease persistent mass effect. Jay Loeffler (Massachusetts General Hospital, Boston, MA, USA) says, “the local control in the series was relatively disappointing considering the radiosurgery was delivered at a time of minimal (if any) residual disease. I would have anticipated a control rate 10–15% higher, which raises the issue if radiation effect was being scored as tumor recurrence”. Soltys adds, however, “the radiation parameters of this technique may be further optimised. In addition to the planned addition of a 2-mm margin, the influence of hypofractionation in three treatment sessions as opposed to a single day of sterotactic radiotherapy will be examined in a pending prospective trial”.
Sally Simpson
Paclitaxel for metastatic germ-cell tumour Inclusion of paclitaxel into the combination of high-dose sequential etoposide, ifosfomide, and cisplatin (VIP) chemotherapy with peripheral blood-derived haemopoetic stem-cell (PBSC) support produces a favourable response in patients with untreated metastatic germ-cell tumours (J Clin Oncol 2007; 25: 5742–47). “We tried to establish the maximal tolerable dose of paclitaxel [plus] high dose VIP, [and] assessed the toxicity, safety, response, and survival in order to improve the treatment of poor-risk germ-cell tumours”, says first author Jörg Hartmann (Eberhard-Karls-University of Tuebingen, Germany). In a combined phase I/II study, researchers enrolled 53 patients with poor prognosis non-seminomatous germ-cell tumours. Initially, all patients received one cycle of standard-dose VIP plus granulocyte colony-stimulating factor to collect autologous PBSCs. 98
Three cycles (range 2–4) of paclitaxel plus high-dose VIP with PBSC support was administered 21 days apart. Paclitaxel was administered in three dose levels (level 1: 135 mg/m²; level 2: 175 mg/m²; level 3: 225 mg/m²). Patients with brain metastasis received concomitant radiotherapy. Orchidectomy was done in newly diagnosed patients and a residual mass, if present, was subsequently resected. Addition of paclitaxel resulted in doseindependent myelosuppression. The median duration of leucocytes <1000/µl and thrombocytes <25 000/µl was 6 and 4 days respectively. WHO grade 2 neurotoxicity and grade 3 encephalopathy were noted in two patients at dose levels 2 and 3. 2-year and 5-year survival was 77·6% (95% CI 65·4–89·9) and 75·2% (62·55–87·8%), respectively. “It is difficult to comment on the utility of adding paclitaxel to the high-
dose VIP regimen for poor-risk nonseminomatous germ-cell tumours in the absence of a randomised trial. Additionally, the value of high-dose VIP as opposed to conventional bleomycin, etoposide, and cisplatin is unproven in this setting”, says Guru Sonpavde (US Oncology Research, Webster, TX, USA). “Given the toxicity profile with high-dose VIP plus paxlitaxel, and the profusion of novel biological agents, such as bevacizumab and sunitinib, another avenue may be to investigate the role of combining these novel biological agents with conventional chemotherapy in the frontline setting”, he adds. “Addition of paclitaxel up to a dose of 225 mg/m² is feasible. Currently, efficacy is being investigated in a larger number of patients in an expanded phase II study”, comments Hartmann.
Kaushal Raj Pandey http://oncology.thelancet.com Vol 9 February 2008
Reducing radiation to the brain
CC Studio/Science Photo Library
Adjuvant stereotactic radiotherapy of the resection cavity for brain metastases compares favourably with postoperative whole-brain irradiation (Int J Radiat Oncol Biol Phys 2008; 70: 187–93). In a retrospective analysis, Scott Soltys and colleagues (Stanford University Medical Center, CA, USA)
Stereotactic radiotherapy of the brain might control local recurrence
identified 72 patients with brain metastases who had been given stereotactic radiotherapy of the resection cavity. Whole-brain irradiation was deferred in each case until local tumour recurrence. Patients received a median marginal dose of 18·0 Gy (range 15·0–30·0), and had a follow-up MRI at 3 months to assess local control. Seven patients died before follow-up; however, all 72 patients were included in the survival analysis. Local control at 6 months and 12 months was 88% and 79%, respectively. For the ten patients who had recurrence, median time-toprogression was 5·7 months (range 3·2–14·2). Median overall survival for all 72 patients was 15·1 months (range 0·8–80·5). Overall survival at 6 months and 12 months was 77% and 57%, respectively. Seven patients had symptomatic post-treatment oedema, three of which
had surgical resection of a region of necrosis to decrease persistent mass effect. Jay Loeffler (Massachusetts General Hospital, Boston, MA, USA) says, “the local control in the series was relatively disappointing considering the radiosurgery was delivered at a time of minimal (if any) residual disease. I would have anticipated a control rate 10–15% higher, which raises the issue if radiation effect was being scored as tumor recurrence”. Soltys adds, however, “the radiation parameters of this technique may be further optimised. In addition to the planned addition of a 2-mm margin, the influence of hypofractionation in three treatment sessions as opposed to a single day of sterotactic radiotherapy will be examined in a pending prospective trial”.
Sally Simpson
Paclitaxel for metastatic germ-cell tumour Inclusion of paclitaxel into the combination of high-dose sequential etoposide, ifosfomide, and cisplatin (VIP) chemotherapy with peripheral blood-derived haemopoetic stem-cell (PBSC) support produces a favourable response in patients with untreated metastatic germ-cell tumours (J Clin Oncol 2007; 25: 5742–47). “We tried to establish the maximal tolerable dose of paclitaxel [plus] high dose VIP, [and] assessed the toxicity, safety, response, and survival in order to improve the treatment of poor-risk germ-cell tumours”, says first author Jörg Hartmann (Eberhard-Karls-University of Tuebingen, Germany). In a combined phase I/II study, researchers enrolled 53 patients with poor prognosis non-seminomatous germ-cell tumours. Initially, all patients received one cycle of standard-dose VIP plus granulocyte colony-stimulating factor to collect autologous PBSCs. 98
Three cycles (range 2–4) of paclitaxel plus high-dose VIP with PBSC support was administered 21 days apart. Paclitaxel was administered in three dose levels (level 1: 135 mg/m²; level 2: 175 mg/m²; level 3: 225 mg/m²). Patients with brain metastasis received concomitant radiotherapy. Orchidectomy was done in newly diagnosed patients and a residual mass, if present, was subsequently resected. Addition of paclitaxel resulted in doseindependent myelosuppression. The median duration of leucocytes <1000/µl and thrombocytes <25 000/µl was 6 and 4 days respectively. WHO grade 2 neurotoxicity and grade 3 encephalopathy were noted in two patients at dose levels 2 and 3. 2-year and 5-year survival was 77·6% (95% CI 65·4–89·9) and 75·2% (62·55–87·8%), respectively. “It is difficult to comment on the utility of adding paclitaxel to the high-
dose VIP regimen for poor-risk nonseminomatous germ-cell tumours in the absence of a randomised trial. Additionally, the value of high-dose VIP as opposed to conventional bleomycin, etoposide, and cisplatin is unproven in this setting”, says Guru Sonpavde (US Oncology Research, Webster, TX, USA). “Given the toxicity profile with high-dose VIP plus paxlitaxel, and the profusion of novel biological agents, such as bevacizumab and sunitinib, another avenue may be to investigate the role of combining these novel biological agents with conventional chemotherapy in the frontline setting”, he adds. “Addition of paclitaxel up to a dose of 225 mg/m² is feasible. Currently, efficacy is being investigated in a larger number of patients in an expanded phase II study”, comments Hartmann.
Kaushal Raj Pandey http://oncology.thelancet.com Vol 9 February 2008