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The authors updated their report on a randomized trial initiated in 1982 comparing, in early breast cancer, high-dose IM Medroxyprogesterone acetate (HD-MPA) adjuvant hormonotherapy during 6 months with no hormonotherapy; node-positive patients also received 6 courses of IV CMF (day 1, day 8; q.4 weeks). 246 node-negative (NN) and 270 node-positive (NP) patients had been followed for a median duration of 13 years. Previous results were confirmed in this analysis on mature data. In NN patients, relapse-free survival (RFS) was improved in the adjuvant hormonotherapy arm, regardless of age while overall survival (OAS) was also increased in younger (less then 50 years) patients. In the whole group of NP patients, no difference was seen regarding RFS or OAS. However, an age-dependant opposite effect was observed: younger patients (< 50) experienced a worse and significant outcome of relapse-free and overall survivals when receiving adjuvant HD-MPA while older patients (> = 50) enjoyed a significant improvement of their relapse-free survival. For both NN and NP patients, differences in overall survivals observed in older women with a shorter follow-up, were no longer detected. [ABSTRACT FROM AUTHOR]

The p73 gene has been mapped to 1p36.33, a region which is frequently deleted in a wide variety of neoplasms including tumours of neuroectodermal origin. The p73 protein shows structural and functional homology to p53. For these reasons,p73 was considered as a positional and functional candidate tumour suppressor gene. Thus far, mutation analysis has provided no evidence for involvement of p73 in oligodendrogliomas, lung carcinoma, oesophageal carcinoma, prostatic carcinoma and hepatocellular carcinoma. In neuroblastoma, two mutations have been observed in a series of 140 tumours. In view of the occurrence of 1p deletions in Merkel cell carcinoma (MCC) and the location of p73 we decided to search for mutations in The p73 gene in five MCC cell lines and ten MCC tumours to test potential tumour suppressor function for this gene in MCC. In view of the possible complementary functions of p73 andTP53 we also examined the status of the TP53 gene. Sequence analysis of the entire coding region of The p73 gene revealed previously reported polymorphisms in four MCCs. In one MCC tumour, a mis-sense mutation located in the NH[SUB2]-terminal transactivation region of the p73 gene was found. These results show that p73, analogous to neuroblastoma, is infrequently mutated in MCC. This is also the first report in which the role of TP53 in MCC has been investigated by sequencing the entire coding region of TP53. TP53 mis-sense mutations and one non-sense mutation were detected in three of 15 examined MCCs, suggesting thatTP53 mutations may play a role in the pathogenesis or progression of a subset of MCCs. Moreover, typical UVB induced C to T mutations were found in one MCC cell line thus providing further evidence for sun-exposure in the aetiology of this rare skin cancer. [ABSTRACT FROM AUTHOR]

Marimastat is a specific inhibitor of matrix metalloproteinases that has been shown to be effective in cancer models. A pilot, escalating-dose study of oral marimastat was performed in patients with recurrent colorectal cancer, in whom evaluation of serological response was made by measurement of carcinoembryonic antigen (CEA) levels. The study assessed the safety and tolerability of 4 weeks administration of marimastat, and determined a dose range producing detectable serological effects. Patients were recruited with a serum CEA level greater than 5 ng ml[SUP-1], and rising by more than 25% over a 4-week screening period. Patients were treated for 28 days and entered into a continuation protocol if a serological response or clinical benefit was observed. Pharmacokinetic and safety data determined that groups of patients were recruited sequentially at 25 mg and 50 mg twice daily, and, thereafter, 10 mg twice daily, 10 mg once daily, 5 mg once daily and 20 mg once daily. A biological effect (BE) was defined as a CEA value on day 28 no greater than on day 0; a partial biological effect (PBE) was defined as a rise in CEA over the 28-day treatment period of less than 25%. Of 70 patients recruited, 63 completed the 28-day treatment period, and 55 were eligible for cancer antigen analysis. Examination of the dose-effect relationships provides evidence for a causal relationship between marimastat and biological effects: the proportion of patients with BE or PBE was higher with twice daily dosing (16 out of 25, 64%) than with once daily dosing (11 out of 30, 37%) (P = 0.043, X[SUP2]test). Furthermore, the median rates of rise of CEA fell markedly during treatment compared with the screening period for patients receiving twice daily marimastat (P < 0.0001), but not for patients receiving marimastat once daily (P = 0.25). Musculoskeletal adverse events emerged as the principal drug-related toxicity of marimastat, occurring in a dose- and time-dependent fashion. It was... [ABSTRACT FROM AUTHOR]

While conventional chemotherapy regimens aim to be cytotoxic against proliferating cells, molecular targeted therapies are directed at specific cancer-associated pathways. To optimize cancer care, an early evaluation of treatment response is warranted for any tumor type - and for any treatment - by using conventional imaging modalities such as ultrasound, CT and MR, FDG-PET or specific radiotracer. FDG-PET is one of the most extensively and successfully used imaging modalities to achieve an early response evaluation. A high SUV-value is a surrogate for malignancy in terms of cancer care and a decrease in FDG-uptake after therapy is associated with treatment response and a favorable clinical outcome. Anyhow, the potential of PET reaches further. By providing metabolic information PET (with or without CT) can help to select patients for targeted therapy and to adapt treatment protocols. PET with FDG and maybe other, more specific PET tracers, promises to direct in a better way personalized cancer care and thus promote translational research. An interesting aspect of molecular imaging is the ability to achieve knowledge on distribution and expression levels of a given receptor. Hereby, imaging could help in guiding systemic treatment given a broad spectrum of radiotracers, detecting specific mutations at molecular level in vivo. From an oncologists point of view the concept of 'personalized medicine' should evolve to include 'personalized imaging' as well as 'personalized treatment' in order to optimize cancer care, reduce side effects and improve quality of life for cancer patients.