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Predicting response to cisplatin in NSCLC
Newsdesk
Bendamustine for advanced sarcoma A phase II trial by German researchers has shown that bendamustine, a bifunctional alkylating drug, shows encouraging results in patients with advanced soft-tissue sarcoma (STS; Cancer, published online June 28, 2007; DOI: 10.1002/cncr.22846). Joerg Hartmann (Eberhard-Karls University, Tuebingen, Germany) and co-workers noted that for patients with advanced STS, although anthracyclines and ifosfamide have substantial single-agent activity, no standard treatment option exists for patients who fail previous treatment with these two drugs. The researchers therefore aimed to assess the efficacy of bendamustine (which shows no cross-resistance with anthracyclines and ifosfamide) in 36 patients with metastatic STS (aged 18–79 years), who were previously treated with anthracyclines or ifosfamide or both.
Most (n=20) of these patients had shown disease progression on previous treatment. Bendamustine was given as second-line treatment in 21 patients and as thirdline treatment in 15. A 30-minute intravenous infusion at a dose of 100 mg/m2 was given on days 1 and 2, repeated every 28 days. A total of 101 cycles of treatment were given (median=2 cycles; range=1–8). One patient achieved partial remission and 11 had stable disease. In an intention-to-treat analysis, progression-free survival was 35·3% (95% CI 19·3–51·3%) at 3 months and 20·6% (7·1–34·1%) at 6 months. Six of the 15 patients who had leiomyosarcoma histology showed disease stabilisation. Toxic effects were mild to moderate. Grade 3 toxic effects (according to the National Cancer Institute Common Toxicity Criteria)
included anaemia in three patients, leucopenia in four patients, and thrombocytopenia, non-neutropenic fever, and an allergic reaction in one patient each. “Bendamustine may be as effective as other compounds but has a more convenient toxicity profile”, says Hartmann. “The drug is well tolerated and has some activity, particularly in patients with leiomyosarcoma histology”, he adds. Gautam Das (Calcutta National Medical College, Calcutta, India) comments, “metastatic STS has a poor prognosis—the median overall survival in patients with metastatic STS is just 1 year, and the treatment options for these patients are also very limited”. Therefore, this study is impressive, but we should wait for the results of a phase III trial, he adds.
Sanjit Bagchi
Predicting response to cisplatin in NSCLC
Alfred Pasieka/Science Photo Library
Patients with non-small-cell lung cancer (NSCLC) whose tumours have low expression of a DNAdamage repair gene, excision repair cross-complementing 1 (ERCC1), responded better to cisplatin-based chemotherapy and lived longer than those with high expression of ERCC1, according to a new study (J Clin Oncol 2007; 25: 2747–54).
Targeting DNA repair could help customise treatment
674
“This is the first randomised phase III study demonstrating that the concept of customised chemotherapy is feasible”, says researcher Rafael Rosell (Catalan Institute of Oncology, Barcelona, Spain). 444 patients with stage IV NSCLC were randomly assigned in a 1:2 ratio to either a control or genotypic group. ERCC1 was then assessed in the genotypic group, and patients were treated according to high or low ERCC1 expression. Those with low expression were assigned cisplatin and docetaxel, patients with high expression were assigned gemcitabine plus docetaxel; the control group were assigned cisplatin and docetaxel. Median overall survival was 10·4 months in patients with low expression, 9·5 months for patients with high expression, and 9·8 months for the control group. Objective response was attained by 53 patients (39·3%) in the control
group and 107 patients (50·7%) in the genotypic group (p=0·02). “We are currently working on trials of customised therapy with BRCA1, a master gene with a much more crucial role in DNA repair”, comments Rosell. “For predicting response to chemotherapy, these genes are not only useful in lung cancer, [but] can be used in the vast majority of malignancies and leukaemias, and in radiotherapy.” “This is a very nicely designed trial that shows how personalising therapy can improve outcomes for patients …using chemotherapy for a disease that kills over 170 000 a year in the USA alone”, says Roy Herbst (MD Anderson Cancer Center, Houston, TX, USA). “If we want to continue to make advances in NSCLC, we will need to apply these and other similar findings to treatment”, continues Herbst.
Vicki Brower http://oncology.thelancet.com Vol 8 August 2007
Bendamustine for advanced sarcoma A phase II trial by German researchers has shown that bendamustine, a bifunctional alkylating drug, shows encouraging results in patients with advanced soft-tissue sarcoma (STS; Cancer, published online June 28, 2007; DOI: 10.1002/cncr.22846). Joerg Hartmann (Eberhard-Karls University, Tuebingen, Germany) and co-workers noted that for patients with advanced STS, although anthracyclines and ifosfamide have substantial single-agent activity, no standard treatment option exists for patients who fail previous treatment with these two drugs. The researchers therefore aimed to assess the efficacy of bendamustine (which shows no cross-resistance with anthracyclines and ifosfamide) in 36 patients with metastatic STS (aged 18–79 years), who were previously treated with anthracyclines or ifosfamide or both.
Most (n=20) of these patients had shown disease progression on previous treatment. Bendamustine was given as second-line treatment in 21 patients and as thirdline treatment in 15. A 30-minute intravenous infusion at a dose of 100 mg/m2 was given on days 1 and 2, repeated every 28 days. A total of 101 cycles of treatment were given (median=2 cycles; range=1–8). One patient achieved partial remission and 11 had stable disease. In an intention-to-treat analysis, progression-free survival was 35·3% (95% CI 19·3–51·3%) at 3 months and 20·6% (7·1–34·1%) at 6 months. Six of the 15 patients who had leiomyosarcoma histology showed disease stabilisation. Toxic effects were mild to moderate. Grade 3 toxic effects (according to the National Cancer Institute Common Toxicity Criteria)
included anaemia in three patients, leucopenia in four patients, and thrombocytopenia, non-neutropenic fever, and an allergic reaction in one patient each. “Bendamustine may be as effective as other compounds but has a more convenient toxicity profile”, says Hartmann. “The drug is well tolerated and has some activity, particularly in patients with leiomyosarcoma histology”, he adds. Gautam Das (Calcutta National Medical College, Calcutta, India) comments, “metastatic STS has a poor prognosis—the median overall survival in patients with metastatic STS is just 1 year, and the treatment options for these patients are also very limited”. Therefore, this study is impressive, but we should wait for the results of a phase III trial, he adds.
Sanjit Bagchi
Predicting response to cisplatin in NSCLC
Alfred Pasieka/Science Photo Library
Patients with non-small-cell lung cancer (NSCLC) whose tumours have low expression of a DNAdamage repair gene, excision repair cross-complementing 1 (ERCC1), responded better to cisplatin-based chemotherapy and lived longer than those with high expression of ERCC1, according to a new study (J Clin Oncol 2007; 25: 2747–54).
Targeting DNA repair could help customise treatment
674
“This is the first randomised phase III study demonstrating that the concept of customised chemotherapy is feasible”, says researcher Rafael Rosell (Catalan Institute of Oncology, Barcelona, Spain). 444 patients with stage IV NSCLC were randomly assigned in a 1:2 ratio to either a control or genotypic group. ERCC1 was then assessed in the genotypic group, and patients were treated according to high or low ERCC1 expression. Those with low expression were assigned cisplatin and docetaxel, patients with high expression were assigned gemcitabine plus docetaxel; the control group were assigned cisplatin and docetaxel. Median overall survival was 10·4 months in patients with low expression, 9·5 months for patients with high expression, and 9·8 months for the control group. Objective response was attained by 53 patients (39·3%) in the control
group and 107 patients (50·7%) in the genotypic group (p=0·02). “We are currently working on trials of customised therapy with BRCA1, a master gene with a much more crucial role in DNA repair”, comments Rosell. “For predicting response to chemotherapy, these genes are not only useful in lung cancer, [but] can be used in the vast majority of malignancies and leukaemias, and in radiotherapy.” “This is a very nicely designed trial that shows how personalising therapy can improve outcomes for patients …using chemotherapy for a disease that kills over 170 000 a year in the USA alone”, says Roy Herbst (MD Anderson Cancer Center, Houston, TX, USA). “If we want to continue to make advances in NSCLC, we will need to apply these and other similar findings to treatment”, continues Herbst.
Vicki Brower http://oncology.thelancet.com Vol 8 August 2007