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Palliation using hypofractionated radiotherapy
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Palliation using hypofractionated radiotherapy Hypofractionated radiotherapy—a form of radiotherapy in which larger doses are used per fraction—shows encouraging results for the palliation of patients with advanced head and neck cancer who are unsuitable for curative treatment (Radiother Oncol 2007; 85: 456–62). “Approximately 30% of head and neck cancer patients presenting to hospitals in developed countries have either incurable disease or are not fit for curative treatment”, says first author Sandro Porceddu (Princess Alexandra Hospital, Brisbane, Australia). “Unfortunately, the median survival of these patients is in the order of 6 months”, he adds. Porceddu and co-workers did a phase II trial, in which 35 patients with incurable squamous-cell carcinoma of the head and neck were assigned to a course of hypofractionated radiotherapy. The radiotherapy
dose was 30 Gy in five fractions administered twice weekly (at least 3 days apart) over 2·5 weeks, with an additional boost of 6 Gy in suitable patients who had small-volume disease (3 cm or less). Of the 35 patients, 27 were eligible for primary-site analysis; 15 had a complete response and five had a partial response. Overall response was 80% (28 of 35). The most common toxic effects were grade 3 mucositis in nine patients and dysphagia in four patients. 21 patients were assessed for quality of life and symptom control; 13 patients had an overall quality of life improvement and 14 reported an improvement in pain. However, progression-free and overall survival remained short, with median time to progression and death at 3·9 months and 6·1 months, respectively. Seven patients survived
beyond 12 months after the conclusion of treatment. “The treatment was well tolerated”, comments Porceddu. He explains, “One of the major benefits of this trial is that the treatment is delivered over a short period of time, which is advantageous for patients, and it utilises very little in the way of radiotherapy resources, which is important for busy and overloaded radiotherapy centres”. “The trial is impressive as it offers an effective palliation for patients with advanced head and neck cancer, with an optimum compliance”, comments Basudeb Bhar (Calcutta Medical Research Institute, Calcutta, India). “However, this regimen should be further tested, preferably in combination with other options, so that it can also have an impact on the patient’s survival.”
Sanjit Bagchi
Combined treatment targets chemorefractory tumours
National Cancer Institute/Science Photo Library
Combined anti-inflammatory and angiostatic treatments that target tumour cells and stromal cells might control chemorefractory malignancies in advanced melanoma (Melanoma Res 2007; 17: 360–64). A randomised multicentre phase II
Targeting the inflammatory tumour microenvironment in metastatic melanoma
16
trial by Albrecht Reichle (University of Regensburg, Germany) and colleagues, shows that progressionfree survival (PFS) is longer with anti-inflammatory plus angiostatic treatment compared with angiostatic treatment alone. “Targeting…the stroma …is a completely new (and cheap) approach”, says Reichle. Of 76 patients with metastatic melanoma, 32 were randomly assigned to trofosfamide (50 mg three times daily) and 35 to trofosfamide plus rofecoxib (25 mg orally, once daily) and pioglitazone (60 mg orally, once daily). Estimated PFS at 1 year was 0% for patients assigned to trofosfamide and 9% for those assigned to the combined treatment. Cox analysis showed a significant effect of antiinflammatory treatment on PFS (p=0·016) and a significant effect of C-reactive protein response on overall survival (p=0·045).
“The idea of targeting the inflammatory tumour microenvironment is interesting and valid. Melanomas make a wide range of cytokines and chemokines. However, it will be important to repeat and extend the trial to a larger number of patients”, says Frances Balkwill (Translational Oncology Laboratory, Cancer Research UK). “These observations are highly interesting and may also be relevant for other progressive tumours”, comments Kent Lundholm (Göteborg University, Sweden). “Several observations suggest that local and systemic inflammation is a driving force in progressive malignancy. However, it is not clear whether inflammation is the primary motor in progression or, rather, a facilitating factor. Irrespective of this, it may be worthwhile to target inflammation during treatment.”
Marta Paterlini http://oncology.thelancet.com Vol 9 January 2008
Palliation using hypofractionated radiotherapy Hypofractionated radiotherapy—a form of radiotherapy in which larger doses are used per fraction—shows encouraging results for the palliation of patients with advanced head and neck cancer who are unsuitable for curative treatment (Radiother Oncol 2007; 85: 456–62). “Approximately 30% of head and neck cancer patients presenting to hospitals in developed countries have either incurable disease or are not fit for curative treatment”, says first author Sandro Porceddu (Princess Alexandra Hospital, Brisbane, Australia). “Unfortunately, the median survival of these patients is in the order of 6 months”, he adds. Porceddu and co-workers did a phase II trial, in which 35 patients with incurable squamous-cell carcinoma of the head and neck were assigned to a course of hypofractionated radiotherapy. The radiotherapy
dose was 30 Gy in five fractions administered twice weekly (at least 3 days apart) over 2·5 weeks, with an additional boost of 6 Gy in suitable patients who had small-volume disease (3 cm or less). Of the 35 patients, 27 were eligible for primary-site analysis; 15 had a complete response and five had a partial response. Overall response was 80% (28 of 35). The most common toxic effects were grade 3 mucositis in nine patients and dysphagia in four patients. 21 patients were assessed for quality of life and symptom control; 13 patients had an overall quality of life improvement and 14 reported an improvement in pain. However, progression-free and overall survival remained short, with median time to progression and death at 3·9 months and 6·1 months, respectively. Seven patients survived
beyond 12 months after the conclusion of treatment. “The treatment was well tolerated”, comments Porceddu. He explains, “One of the major benefits of this trial is that the treatment is delivered over a short period of time, which is advantageous for patients, and it utilises very little in the way of radiotherapy resources, which is important for busy and overloaded radiotherapy centres”. “The trial is impressive as it offers an effective palliation for patients with advanced head and neck cancer, with an optimum compliance”, comments Basudeb Bhar (Calcutta Medical Research Institute, Calcutta, India). “However, this regimen should be further tested, preferably in combination with other options, so that it can also have an impact on the patient’s survival.”
Sanjit Bagchi
Combined treatment targets chemorefractory tumours
National Cancer Institute/Science Photo Library
Combined anti-inflammatory and angiostatic treatments that target tumour cells and stromal cells might control chemorefractory malignancies in advanced melanoma (Melanoma Res 2007; 17: 360–64). A randomised multicentre phase II
Targeting the inflammatory tumour microenvironment in metastatic melanoma
16
trial by Albrecht Reichle (University of Regensburg, Germany) and colleagues, shows that progressionfree survival (PFS) is longer with anti-inflammatory plus angiostatic treatment compared with angiostatic treatment alone. “Targeting…the stroma …is a completely new (and cheap) approach”, says Reichle. Of 76 patients with metastatic melanoma, 32 were randomly assigned to trofosfamide (50 mg three times daily) and 35 to trofosfamide plus rofecoxib (25 mg orally, once daily) and pioglitazone (60 mg orally, once daily). Estimated PFS at 1 year was 0% for patients assigned to trofosfamide and 9% for those assigned to the combined treatment. Cox analysis showed a significant effect of antiinflammatory treatment on PFS (p=0·016) and a significant effect of C-reactive protein response on overall survival (p=0·045).
“The idea of targeting the inflammatory tumour microenvironment is interesting and valid. Melanomas make a wide range of cytokines and chemokines. However, it will be important to repeat and extend the trial to a larger number of patients”, says Frances Balkwill (Translational Oncology Laboratory, Cancer Research UK). “These observations are highly interesting and may also be relevant for other progressive tumours”, comments Kent Lundholm (Göteborg University, Sweden). “Several observations suggest that local and systemic inflammation is a driving force in progressive malignancy. However, it is not clear whether inflammation is the primary motor in progression or, rather, a facilitating factor. Irrespective of this, it may be worthwhile to target inflammation during treatment.”
Marta Paterlini http://oncology.thelancet.com Vol 9 January 2008