mitomycin Classic KS predominantly affects elderly
Classic KS predominantly affects elderly people over 50 years, many of whom do not tolerate aggressive chemotherapy regimens well due to frequent comorbidity and diminished cardiovascular and bone marrow reserves. Classic KS follows an indolent course (average survival is 10–15 years) requiring long-term and repeated chemotherapy. Therefore, lowering the toxicity of docetaxel without compromising the efficacy for elderly patients was investigated.
Phase 2 and 3 studies have demonstrated that weekly docetaxel in metastatic breast carcinoma had less toxicity including neutropenia or febrile neutropenia, in comparison with 3-weekly docetaxel. Lim et al used docetaxel at 25 mg/m in advanced-stage AIDS-associated KS and reported 42% partial response rate with 33% Grade 3 neutropenia and no Grade 4 toxicity. By contrast to classic KS, AIDS associated KS patients are immunocompromised. In light of this, we speculated that weekly docetaxel in classic KS could potentially offer a better outcome with fewer side effects than in AIDS-associated KS.
In our case report, weekly docetaxel 30 mg/m in an elderly patient with refractory classic KS offered a complete response as well as improvement of performance status. To our knowledge, this is the first case report to address the use of weekly docetaxel (30 mg/m) in classic KS.
Another question raised from our case report is “how many doses of docetaxel are appropriate in classic KS to obtain maximum effect with minimum toxicity?” A study by Vacca et al showed very low docetaxel and paclitaxel doses selectively causes organic and functional damage of endothelial mitomycin of KS and that docetaxel is four times stronger. In our case, only six doses of weekly docetaxel (total dose was 180 mg/m) gave the patient durable remission. The total dose of 180 mg/m was consistent with another case detailing a complete response for every 3 week dosing for classic KS by Stoebner et al and a case by Fardet which generated a 20-month remission of classic KS lesions. The total number of doses for docetaxel to achieve the most effective response in this setting is not well understood, however limited pilot data suggests a low dose of docetaxel may produce good effects with low toxicity. Neurotoxicity in particular appears to be dose dependent, which will impact repeated delivery of docetaxel.
Dyschromatosis symmetrica hereditaria (DSH, Online Mendelian Inheritance in Man 127400) is a rare autosomal dominant pigmentary disorder characterized by intermingled hyper- and hypopigmented macules on the face and the dorsal aspects of the extremities with onset during infancy or early childhood. DSH had been reported primarily in Japan, Taiwan, and China. Mutations in the RNA-specific adenosine deaminase 1 () gene are known to be responsible for the disorder. To date, more than 120 mutations in the gene associated with the disorder have been reported. Here we report a novel mutation of c.1944C>G (p.Y648X) in a Taiwanese patient with DSH and a Becker\'s nevus-like lesion on the buttock. A 13-year-old male patient presented to our clinic with reticulate hyper- and hypopigmented macules on the dorsal aspect of the hands progressively for 4 years (A). Mild lesions with off-white macules on the dorsal feet were also noted. There were also some freckle-like macules scattered on the face and neck. In addition, one brown hairy pigmented plaque on the left buttock, which occurred gradually at age 10 years, was noted during examination. The clinical features suggested a Becker\'s nevus-like lesion (B), however, the diagnosis was not confirmed by histopathology. There was no family history of DSH. Genomic DNA was extracted from the whole blood samples of the patient and his parents with informed consent. All exons of the gene, including intron–exon boundaries, were amplified using polymerase chain reaction. A novel nonsense mutation c.1944C>G (p.Y648X) in exon 5 of the gene was identified (). , also called (double-stranded RNA specific adenosine deaminase), spans 26,191 bp of genomic sequence on chromosome 1q21.3, and contains 15 exons. ADAR1 is a modular protein with a C-terminal deaminase catalytic domain, three centrally located dsRNA-binding domains (dsRBDs) and one or two N-terminal Z-DNA–binding domains. The mutation (p.Y648X) in exon 5 identified in the present case leads to a premature termination codon with incomplete dsRNA-binding motif and loss of adenosine deaminase domain. Previous studies indicate that both the deaminase domain and the dsRNA-binding domain are important for exerting ADAR1 catalytic activity.