Cancer Research UK procedures in manufacture and toxicology of radiotracers intended for Pre-phase I positron emission tomography studies in cancer patients

Radiolabelled compounds formulated for injection (radiopharmaceuticals), are increasingly being employed in drug development studies. These can be used in tracer amounts for either pharmacokinetic or pharmacodynamic studies. Such radiotracer studies can also be carried out early in man, even prior to conventional Phase I clinical testing. The aim of this document is to describe procedures for production and safety testing of oncology radiotracers developed for imaging by positron emission tomography in cancer patients. We propose strategies for overcoming the inability to produce compounds in sufficient quantities via the radiosynthetic routes for full chemical characterisation and toxicology testing including (i) independent confirmation as far as possible that the stable compound associated with the radiopharmaceutical is identical to the non-labelled compound, (ii) animal toxicity studies with ⩾10 times (typically 100 times) the intended tracer dose in humans scaled by body surface area, and (iii) patient monitoring during the radiotracer positron emission tomography clinical trial

Cancer drug development in Europe: A selection of new agents under development at the European Drug Development Network

From may 99, three european leaders in anti-cancer drug development (EORTC, Cancer Research UK, SENDO) have got together to form a network of collaborating groups: the European Drug Development Network. The member organisations hake all agreed to join their efforts in developing new drugs. They have acquired a great and efficient expertise in anticancer drug development covering all aspects from drug screening to refinement of trial methodology and translational research. In this paper, the most interesting drugs under development in each of the three organisations are being described and discussed

Phase II studies of polymer-doxorubicin (PK1, FCE28068) in the treatment of breast, lung and colorectal cancer

Phase I studies of [N-(2-hydroxypropyl)methacrylamide] (HPMA) copolymer-doxorubicin previously showed signs of activity coupled with 5-fold decreased anthracycline toxicity in chemotherapy-refractory patients. Here we report phase H studies using a similar material (FCE28068) in patients with breast (n=17), non-small cell lung (NSCLC, n=29) and colorectal (n=16) cancer. Up to 8 courses of PK1 (280 mg/m(2) doxorubicin-equivalent) were given i.v., together with I-123-labelled imaging analogue. Toxicities were tolerable, with grade 3 neutropenia more prominent in patients with breast cancer (4/17, 23.5% compared with 5/62, 8.1% overall). Of 14 evaluable patients with breast cancer 3 had partial responses (PR), all anthracycline-naive patients. In 26 evaluable patients with NSCLC, 3 chemotherapy-naive patients had PR. In contrast, none of the 16 evaluable patients with colorectal cancer responded. Imaging of 16 patients (5 with breast cancer, 6 NSCLC, 5 colorectal cancer) showed obvious tumour accumulation in 2 metastatic breast cancers, although unfortunately no images were obtained from patients who responded. These results show 6/62 PR with limited side effects, Supporting the concept that polymer-bound therapeutics can have modified and improved anticancer activities and suggesting the approach should be explored further for breast cancer and NSCLC