RESUMEN
Cocrystallization of the drug-drug salt-cocrystal of the histone deacetylase inhibitor (HDACi) panobinostat (PAN) and b-rapidly accelerated fibrosarcoma (BRAF) inhibitor dabrafenib (DBF) afforded single crystals of a two-drug salt stabilized by N+-H···O and N+-H···N- hydrogen bonds between the ionized panobinostat ammonium donor and dabrafenib sulfonamide anion acceptor in a 12-member ring motif. A faster dissolution rate for both drugs was achieved through the salt combination compared to the individual drugs in an aqueous acidic medium. The dissolution rate exhibited a peak concentration (Cmax) of approximately 310 mg cm-2 min-1 for PAN and 240 mg cm-2 min-1 for DBF at a Tmax of less than 20 min under gastric pH 1.2 (0.1 N HCl) compared to the pure drug dissolution values of 10 and 80 mg cm-2 min-1, respectively. The novel and fast-dissolving salt DBF-·PAN+ was analyzed in BRAFV600E melanoma cells Sk-Mel28. DBF-·PAN+ reduced the dose-response from micromolar to nanomolar concentrations and lowered IC50 (21.9 ± 7.2 nM) by half compared to PAN alone (45.3 ± 12.0 nM). The enhanced dissolution and lower survival rate of melanoma cells show the potential of novel DBF-·PAN+ salt in clinical evaluation.
RESUMEN
BACKGROUND: Bullous pemphigoid is an uncommon dermatologic manifestation seen in squamous cell lung cancer, and evidence guiding optimal treatment, especially in the elderly population, is limited. We report herein a case of squamous cell lung cancer diagnosed after being investigated for refractory bullous pemphigoid showing marked response to carboplatin-based chemotherapy. This is the first case report that shows carboplatin can be used as an effective alternative in treatment of malignancy-associated bullous pemphigoid. CASE REPORT: An 80-year-old caucasian man developed extensive vesiculobullous rashes on his trunk, chest, abdomen, and inguinal region associated with significant pruritus causing sleep disturbance. The diagnosis of bullous pemphigoid was confirmed on skin biopsy. The skin lesions continued to worsen even after use of oral and topical steroid in addition to oral doxycycline. Chest computed tomography revealed a spiculated left lung lesion along with mediastinal lymphadenopathy. Fine-needle aspiration from the mediastinal lymph node confirmed metastatic squamous cell lung carcinoma. Carboplatin with gemcitabine was initiated, and significant response was seen within 3 days of chemotherapy. The skin lesions continued to remain in remission even after stopping the chemotherapy. CONCLUSION: Although there are still controversies regarding paraneoplastic etiology of bullous pemphigoid, this case presents a temporal association. It is the first case report showing a remarkable response with the use of a carboplatin-based regimen.