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Background:This study was aimed to develop a new method for personalising chemotherapeutic and granulocyte colony-stimulating factor (G-CSF) combined schedules, and use it for suggesting efficacious chemotherapy with reduced neutropenia.Methods:Clinical data from 38 docetaxel (Doc)-treated metastatic breast cancer patients were employed for validating a new pharmacokinetic/pharmacodynamics model for Doc, combined with a mathematical model for granulopoiesis. An optimisation procedure was constructed and used for selecting improved treatment schedules.Results:The combined model accurately predicted observed nadir timing (r=0.99), grade 3 or 4 neutropenia (86% success) and neutrophil counts over time in individual patients (r=0.63), and showed robustness to CYP3A-induced variability in Doc clearance. For average patients, the predicted optimal support for the standard chemotherapy regimen, Doc 100 μg m−2 tri-weekly, is G-CSF, 300 μg, Q1D × 3, starting day 7 post-Doc. This regimen largely moderates chemotherapy-induced neutrophil nadir and neutropenia duration. The more intensive Doc dose, 150 mg m−2, is optimally supported by the slightly less cost-effective G-CSF 300 μg, Q1D × 4, 5 days post-Doc. The latter regimen is optimal for borderline patients (2000 neutrophils per μl) under Doc, 100-150 mg m−2 tri-weekly.Conclusions:The new computational method can serve for tailoring efficacious cytotoxic and supportive treatments, minimising side effects to individual patients. Prospective clinical validation is warranted. [ABSTRACT FROM AUTHOR]

Background : Paclitaxel and trastuzumab are new treatments for patients with metastatic breast cancer. Case report : We describe here a 40-year-old female patient with metastatic breast cancer who developed a photosensitive rash 1 month after initiation of paclitaxel and trastuzumab therapy. The eruption appeared on the dorsal aspect of her hands, forearms, legs and face and consisted of erythema, edema and vesicles, and was associated with distal onycholysis. Aberrations in various parameters of the metabolism of porphyrins were observed in urine and erythrocytes. Sun avoidance and withdrawal of paclitaxel was followed by resolution of the rash and a return to the normal pattern of porphyrins biosynthesis. Conclusion : The combination of paclitaxel and trastuzumab treatment and sun exposure may induce a photosensitive reaction, associated with changes in various parameters of porphyrins biosynthesis. [ABSTRACT FROM AUTHOR]