History
Vinorelbine was invented by the pharmacist Pierre Potier and his team from the CNRS in France in the 1980s and was licensed to the oncology department of the Pierre Fabre Group. The drug was approved in France in 1989 under the brand name Navelbine for the treatment of non-small cell lung cancer. It gained approval to treat metastatic breast cancer in 1991. Vinorelbine received approval by the United States Food and Drug Administration (FDA) in December 1994 sponsored by Burroughs Wellcome Company. Pierre Fabre Group now markets Navelbine in the U.S., where the drug went generic in February 2003. In most European countries, vinorelbine is approved to treat non-small cell lung cancer and breast cancer. In the United States it is approved only for non-small cell lung cancer. Sources
The Madagascan periwinkle Catharanthus roseus L. is the source for a number of important natural products, including catharanthine and vindoline and the vinca alkaloids it produces from them: leurosine and the chemotherapy agents vinblastine and vincristine, all of which can be obtained from the plant. The newer semi-synthetic chemotherapeutic agent vinorelbine, which is used in the treatment of non-small-cell lung cancer and is not known to occur naturally. However, it can be prepared either from vindoline and catharanthine or from leurosine, in both cases by synthesis of anhydrovinblastine. The leurosine pathway uses the Nugent–RajanBabu reagent in a highly chemoselective de-oxygenation of leurosine. Anhydrovinblastine is then reacted sequentially with N-bromosuccinimide and trifluoroacetic acid followed by silver tetrafluoroborate to yield vinorelbine.
This could potentially be of importance in genetically differentiating between NFJS and DPR.The disruption of the KRT14 gene in DPR suggests this gene is important during the early development of dermatoglyphics and sweat glands. Because of the aforementioned genetic similarity between NFJS and DPR, some researchers have suggested treating the disorders as a single condition. Diagnosis
Diagnosis of DPR begins with review of a patients medical history, laboratory results, and clinical examination of symptoms. Biopsy and histopathological examination can be used to test for the presence of hyperkeratosis, parakeratosis, follicular plugging, and basal cell melanization, all indicators of DPR. Furthermore, abnormalities in skin pigmentation patterns as well as the presence of palmoplantar keratoderma with yellow tinting of the skin can indicate a possible case of DPR. Despite the presence of outward indicators, routine blood testing will not yield abnormal results. While the aforementioned symptoms of DPR are outwardly identifiable, DPR is a rare genetic disease that requires genetic analysis to yield a confirmed diagnosis.The Genetic Testing Registry lists 15 clinical genetic tests used in obtaining a diagnosis of this disorder. Two of these tests utilize Targeted Variant Analysis, thirteen utilize sequence analysis of the entire coding region, and seven utilize deletion and duplication analysis. The type of test ordered may depend on the clinicians judgement or access to specific testing methods. Management
To date, there is no medical treatment specific to DPR, however symptom management of palmoplantar hyperkeratosis as well as other, secondary symptoms is possible through the use of topical steroids, keratolytics, and emollients.