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Gan To Kagaku Ryoho 2003 Jan;30(1):105-9

Weekly administration of paclitaxel and pirarubicine for recurrent breast cancer


The therapeutic efficacy of weekly coadministration of paclitaxel (TXL) and pirarubicin (THP) on docetaxel (TXT)- and epirubicin-resistant recurrent breast cancer, adverse reactions caused by this therapy, and the possibility of ambulatory treatment using it were evaluated. The present study was conducted in 11 patients with recurrent breast cancer with pretreatment with CEF and TXT. The site of recurrence was the lung in 9 patients, lymphnodes in 2, bones in 1, liver in 1 and local foci in 1. One cycle consisted of 20 mg/m2 of THP followed by 80 mg/m2 of TXL 4 h later, repeated three times every other week. Three to six cycles were conducted in each patient. An anti-emetic drug was administered before administration of THP as short premedication. Dexamethasone (16 mg; i.v.) and d-chlorpheniramine maleate (12 mg; p.o.) were administered 1 h before administration of TXL and ranitidine (100 mg; i.v.) was administered 30 min before administration of TXL. Ubidecarenone (30 mg/day; p.o.) was administered for 3 days. The response rate was 27.3% with a rating of PR in 3 patients, NC in 6, and PD in 2. Adverse reactions observed included transient facial hot flushes, alopecia grade 1 or milder grade 1 symptoms, and peripheral nerve damage. No adverse reactions such as myocardial disorders or congestive heart failure were noted. Grade 3 and grade 2 neutropenia occurred in 1 and 6 patients, respectively, and 4 patients were admitted for treatment of this. In conclusion, the short premedication was useful, and this was thought to make it possible to conduct ambulatory treatment with TXL + THP in some patients. The response rate of 27.3%, however, was not satisfactory. It will be necessary to clarify the characteristics of this therapy by administering it to a wider spectrum of patients.


J Invest Dermatol 2003 Jan;120(1):27-35

Fas and c-kit are involved in the control of hair follicle melanocyte apoptosis and migration in chemotherapy-induced hair loss.


Chemotherapy alters the structure and function of hair follicle melanocytes. Molecular mechanisms controlling melanocyte responses during chemotherapy-induced hair loss, however, remain largely unknown. Using immunohistology and multicolor confocal microscopy, we show here that cyclophosphamide administration to C57BL/6 mice alters the activity and fate of hair follicle melanocytes. After 24-48 h, hair bulb melanocytes expressing Fas undergo apoptosis. The number of apoptotic follicular melanocytes is significantly reduced (p<0.01) in cyclophosphamide-treated Fas knockout mice compared to wild-type controls, suggesting that Fas signaling contributes to chemotherapy-induced melanocyte death. After 3-5 d, surviving hair bulb melanocytes express c-kit receptor, proliferate, and appear to migrate up the outer root sheath. Tyrosinase-positive and melanogenically active cells then appear in the epidermis. By Western blotting and immunohistochemistry, expression levels of the c-kit ligand, stem cell factor, in skin and epidermis are strongly increased after cyclophosphamide treatment. Cyclophosphamide-induced migration of the hair follicle melanocytes into epidermis is completely abrogated by administration of c-kit neutralizing antibody. These data suggest that chemotherapy induces a complex response in the hair follicle melanocytes, which includes apoptosis, proliferation, and migration. Pharmacologic manipulation of Fas and c-kit signaling pathways might be useful for the correction of skin hyperpigmentation as a side-effect of chemotherapy.


Dermatology 2002;204(1):33-6

Perception of baldness and hair density.


BACKGROUND: Androgenetic alopecia needs to be scored precisely. OBJECTIVE: A possible measure is the ratio between the hair density in the parietal area and that in the occipital area which, being not affected by baldness, supposedly has a 'normal' density. METHODS: On the vertex and just below the occipital protuberance of 109 men, two 1-cm(2) areas were identified. In both areas, hairs were clipped short and photographed by a videomicroscope. Hairs were then counted within a 30-mm(2)-wide central square section. RESULTS: In the occipital area, the average count was 127/cm(2), without differences among the Hamilton/Norwood classes. In the parietal area, the average density significantly diminished from 138 to 47/cm(2). A main difference was found between classes 1-3 vertex and classes 4-6. CONCLUSIONS: The parietal/occipital ratio decreased significantly only when baldness was clinically manifest. The parietal/occipital ratio cannot be a better measure of baldness severity than the rough Hamilton/Norwood scale. The perception of early baldness does not depend on the diminished hair density, but also on the progressive thinning of the hair shafts.


Schweiz Rundsch Med Prax 2001 Nov 29;90(48):2087-93

Photographic documentation of the effectiveness of 1 mg. oral finasteride in treatment of androgenic alopecia in the man in routine general practice in Switzerland


A 6-month, prospective, open, multicenter cohort study in 265 men with male pattern hair loss treated with oral finasteride 1 mg/day (Propecia) was conducted in the office of 52 Swiss dermatologists. The patient's head was placed in a stereotactic device, and Polaroid photographs were taken of the vertex and frontal areas. Endpoints used to determine treatment efficacy were patient self-assessment, investigator clinical assessment, and blinded assessment of the serial Polaroid photographs by a panel of 2 experienced dermatologists. Significant improvements were stated on the photographs by both clinical investigators and the blinded expert panel: 54% of patients showed improvement of hair growth at 6 months of treatment in the vertex region, and 48.7% in the frontal area. No progression of hair loss was found in an additional 38% (vertex) and 47% (frontal region), respectively. Clinical investigator and expert assessment yielded comparable results. Independently, patient self-assessment and investigator clinical assessment confirmed the progress. Propecia was well-tolerated, and no significant safety concerns were identified during the study. The photographic method was well accepted by the physicians. The office-based Polaroid photographic system allowed reliable assessment of change during treatment of male pattern hair loss with Propecia. The data generated in this manner corresponded to the antecedent results of the multicenter, placebo-controlled studies with oral finasteride.


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