NEW YORK (Reuters Health) Aug 01 - In a phase II trial, cetuximab was a promising first-line therapy for unresectable squamous cell carcinoma of the skin (SCCS), French researchers reported online today in the Journal of Clinical Oncology.
Cetuximab blocks epidermal growth factor receptor (EGFR), which is expressed in SCCS.
Most of the 200,000 to 300,000 new cases in the US each year can be managed with surgical excision or radiotherapy, but some are too advanced.
In the first trial of targeted therapy for unresectable SCC of the skin, the researchers gave weekly cetuximab infusions (median, 15 infusions) to 36 patients with chemotherapy-na�ve unresectable SCCS. The median patient age was 79; 23 were older than 70.
Thirty-one patients were evaluable for tumor response at six weeks, said lead author Dr. Eve Maubec from Hopital Bichat in Paris and colleagues.
The disease control rate at week six was 69% (81% among evaluable patients).
Two patients achieved complete responses that lasted for two and a half years after treatment stopped. The best overall response rate (complete and partial remissions) was 28% (10/36).
Three patients with partial or minor responses to cetuximab underwent complementary surgical excision which resulted in persistent freedom from disease for three years in one patient, and local or regional relapse in two patients at seven months and twenty-four months.
Mean overall survival was 8.1 months and estimated survival at week 48 was 52%. Median progression-free survival was 4.1 months.
The 25 patients with disease control at week six maintained that control for a median of five months.
The median duration of response for the 10 patients who achieved complete or partial remission was 6.8 months.
All 36 patients had side effects consistent with those previously reported for cetuximab. Most frequent was an acne-like rash (grade 1 or 2 in 27/31 patients) that appeared a median 14 days into treatment.
The rash was not significantly associated with disease control at week six. However, patient who developed the rash had a significantly prolonged median progression-free survival (4.5 vs. 1.7 months; p=0.004) and a trend toward longer mean overall survival (8.9 vs. 4 months; p=0.054) compared with patients who did not develop the rash.
Dr. Maubec told Reuters Health in an email that cetuximab might be especially useful in elderly patients for whom chemotherapy is not appropriate.
Along with cetuximab and other EGFR inhibitors, alternatives for unresectable SCCS include cisplatin based chemotherapy and other conventional chemotherapy, retinoids, and interferon alpha, Dr. Maubec said.
These tumors are attractive targets for EGFR inhibition because RAS mutations are infrequent, the authors say in their report. Dr. Maubec added, however, that we still need to find biological factors that will predict response.
"A randomized phase III trial is warranted to confirm that cetuximab may be considered as a therapeutic option in this setting, particularly for elderly patients in whom chemotherapy is not appropriate," the research team concludes.
SOURCE: http://bit.ly/qulKuC
J Clin Oncol 2011.
Cetuximab blocks epidermal growth factor receptor (EGFR), which is expressed in SCCS.
Most of the 200,000 to 300,000 new cases in the US each year can be managed with surgical excision or radiotherapy, but some are too advanced.
In the first trial of targeted therapy for unresectable SCC of the skin, the researchers gave weekly cetuximab infusions (median, 15 infusions) to 36 patients with chemotherapy-na�ve unresectable SCCS. The median patient age was 79; 23 were older than 70.
Thirty-one patients were evaluable for tumor response at six weeks, said lead author Dr. Eve Maubec from Hopital Bichat in Paris and colleagues.
The disease control rate at week six was 69% (81% among evaluable patients).
Two patients achieved complete responses that lasted for two and a half years after treatment stopped. The best overall response rate (complete and partial remissions) was 28% (10/36).
Three patients with partial or minor responses to cetuximab underwent complementary surgical excision which resulted in persistent freedom from disease for three years in one patient, and local or regional relapse in two patients at seven months and twenty-four months.
Mean overall survival was 8.1 months and estimated survival at week 48 was 52%. Median progression-free survival was 4.1 months.
The 25 patients with disease control at week six maintained that control for a median of five months.
The median duration of response for the 10 patients who achieved complete or partial remission was 6.8 months.
All 36 patients had side effects consistent with those previously reported for cetuximab. Most frequent was an acne-like rash (grade 1 or 2 in 27/31 patients) that appeared a median 14 days into treatment.
The rash was not significantly associated with disease control at week six. However, patient who developed the rash had a significantly prolonged median progression-free survival (4.5 vs. 1.7 months; p=0.004) and a trend toward longer mean overall survival (8.9 vs. 4 months; p=0.054) compared with patients who did not develop the rash.
Dr. Maubec told Reuters Health in an email that cetuximab might be especially useful in elderly patients for whom chemotherapy is not appropriate.
Along with cetuximab and other EGFR inhibitors, alternatives for unresectable SCCS include cisplatin based chemotherapy and other conventional chemotherapy, retinoids, and interferon alpha, Dr. Maubec said.
These tumors are attractive targets for EGFR inhibition because RAS mutations are infrequent, the authors say in their report. Dr. Maubec added, however, that we still need to find biological factors that will predict response.
"A randomized phase III trial is warranted to confirm that cetuximab may be considered as a therapeutic option in this setting, particularly for elderly patients in whom chemotherapy is not appropriate," the research team concludes.
SOURCE: http://bit.ly/qulKuC
J Clin Oncol 2011.
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