Summary EGFR overexpression in salivary gland carcinomas provides the rational for the investigation of anti-EGFR treatments in recurrent and/or metastatic salivary gland cancers (RMSGCs). The ...activity of cetuximab in terms of clinical benefit rate (CBR) defined as the occurrence of objective response (CR or PR) or stable disease (SD) for ⩾6 months was investigated. From April to December 2005, 30 patients 23 adenoid cystic carcinoma (ACC) and 7 non-ACC were treated with cetuximab at 400 mg/m2 /week followed by 250 mg/m2 /week until progression, major toxicity or voluntary discontinuation. EGFR expression and gene status were retrospectively analyzed by immunocytochemistry and fluorescence in situ hybridization, respectively. A median of 14 courses of cetuximab (range 5–54) were infused. Skin toxicity was the main adverse event. Cetuximab provides a CBR in 50% (95% CL, 31 to 69%) of cases. None tumor sample showed EGFR gene amplification and an increased EGFR copy number was observed in 12% of samples, all ACC. Skin rash ⩾G2, EGFR overexpression and EGFR copy number were not statistically correlated to CB. In RMSGCs further evaluations of EGFR targeting agents are advisable and should take place by appropriate tumor biological selection, differentiating ACC from non-ACC.
The purpose of this article is to present some of the challenges the trial statistician meets when designing a clinical trial of the head and neck cancer. In recent years, the field of head and neck ...cancer has been facing some exciting evolutions, such as the arrival of newly targeted therapies and findings of disease causality and prognosis. These evolutions are accompanied by challenges in trial methodology that continue even today, and will most likely grow in importance in the future. This article focuses essentially on the design of phase III trials and discusses three major topicsshould the trial be designed for a broad or a targeted population? Is there a concern for lack of equipoise and if so, how will it affect the trial results? What are the key elements that need to be taken into consideration when choosing, defining, and measuring the primary endpoint?
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Background: EGFR is expressed in 70% of salivary gland carcinomas (SGC). Investigations of anti EGFR treatment seems rational. Aim: To assess activity of C225 in patients with ...RMSGCs in terms of clinical benefit (CB), defined as occurrence of objective response (CR or PR) or stable disease (SD) for at least 6 months. To correlate treatment outcome with skin toxicity degree and EGFR analysis. Methods: One prior chemotherapy regimen was allowed, except for pts with adenoid cystic carcinoma (ACC) and acinic cell carcinoma for whom 2 lines were allowed. Prior exposure to targeted treatment was not allowed. C225 (Erbitux) was administered iv weekly at 400 mg/mq followed by 250 mg/mq until disease progression, major toxicity or voluntary discontinuation. MRI or CT and PET scan were performed every 6 weeks q4, and q12 thereafter. RECIST response criteria and CTC 3.0. were adopted. Results: From April to December 2005, 30 RMSGCs pts (20 F/10 M; median age 50 yrs), 50% with major SGC, were enrolled. Histotypes were: 23 ACC; 2 mucoepidermoid; 3 myoephitelial; 1 cystadenocarcinoma and 1 acinic cell carcinoma. Thirteen pts (43%) received prior chemotherapy. Localregional (LR) and metastatic (M) disease was present in 13 cases, M in 12, and LR in 5. A median number of 11 drug administration (range 2–31) was given. G2 skin toxicity was recorded in 24 cases. G2 fatigue in 2. At a median FU of 6 months (range 0–8), 2 pts died of PD. Of 22 pts evaluable for response with ≥ 3 months of potential FU, there were 11 SD, 9 PD, while 2 pts refused to continue after 1 months. Currently, 7 of these pts are progression-free at ≥ than 6 months, qualifying for CB definition according to study protocol. Preliminary EGFR analysis showed a high or intermediate expression score in 5 (3 ACC, 1 acinic cell, 1 cistoadenocarcinoma) out of 7 cases, no gene amplification nor chromosome 7 polisomy were found in 3 of 3 analysed ACC. PET results are under evaluation. Conclusions: Hints of activity of C225 in RMSGCs were observed. The early analysis for the CB rate in 23 pts is planned for April 2006, when all of them will have a potential follow-up of ≥ 6 months, and results thereof will be reported.
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Previous reports demonstrate a circadian rhythm of the free thyroid hormones in healthy subjects. In this study we evaluated circadian variation of FT3 and FT4 in hyperthyroid and hypothyroid states. ...We considered six hyperthyroid patients, six hypothyroid patients and six control subjects. Blood samples were taken two hours apart from a catherterized arm vein. Data were evaluated by Halberg's cosinor analysis. The results show that FT3 and FT4 exhibit a circadian rhythm in healthy subjects, not evident in hyperthyroid and hypothyroid patients.
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