Faculty Bibliography
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Antibody-drug conjugates (ADCs) are comprised of a highly potent chemotherapeutic agent linked to a monoclonal antibody directed toward an antigen with high tumor expression. At present, two ADCs are FDA-approved and clinically available, both containing highly potent cytotoxic agents based on picomolar potency of the chemotherapeutic component. Sacituzumab govitecan (IMMU-132) is a novel ADC comprised of a humanized IgG monoclonal antibody (hRS7) specific for trophoblast cell-surface antigen (Trop-2, formerly called EGP-1) conjugated to SN-38, the active metabolite of irinotecan (CPT-11). Sacituzumab govitecan delivers SN-38, a topoisomerase I inhibitor, to tissues enriched in Trop-2. Increased expression of Trop-2 has been demonstrated in multiple solid malignancies of epithelial origin. In a phase I clinical trial of sacituzumab govitecan in patients with various tumor types, tolerability was established at a dose of 10 mg/kg given on days 1 and 8 of 21-day cycles. Potential toxicities are similar to those of irinotecan, principally neutropenia and diarrhea, although diarrhea may be milder due to a reduction in the glucuronidated form of SN-38. While phase II studies are ongoing, interim analyses demonstrate promising activity in highly pretreated populations with a number of metastatic tumor types, including triple-negative breast cancer (TNBC), lung cancer, and urothelial cancer. In February 2016, sacituzumab govitecan received breakthrough therapy designation from the FDA for the treatment of patients with metastatic TNBC.
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Total Results:
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Sacituzumab govitecan Trop-2-targeted antibody-drug conjugate Treatment of epithelial cancers
ISI:000398938300002
ISSN: 0377-8282
CID: 3218112
Clinical reasoning: a middle-aged woman with progressive symmetric weakness and a CSF pleocytosis [Case Report]
PMID: 22474301
ISSN: 1526-632x
CID: 2415312
Journal of acquired immune deficiency syndromes. JAIDS. 2012:59(3):259-65.DOI: 10.1097/QAI.0b013e3182437469
Electrocautery ablation of high-grade anal squamous intraepithelial lesions in HIV-negative and HIV-positive men who have sex with men
BACKGROUND:Anal squamous cell carcinoma (ASCC) incidence has been rising over the past decade, most dramatically in HIV-positive men who have sex with men (MSM). We aimed to identify a novel in-office approach for ablating high-grade anal intraepithelial neoplasia (HGAIN), the believed precursor lesion to ASCC. MATERIALS AND METHODS/METHODS:We performed a retrospective analysis of medical records from a New York City surgical practice, identifying patients with HGAIN treated with electrocautery ablation (ECA) and followed for at least 5 months with high-resolution anoscopy, biopsies, and/or cytology. We sought to determine HGAIN recurrence and progression to ASCC after ECA. RESULTS:Two hundred thirty-two MSM, 132 HIV positive and 100 HIV negative, with median follow-up of 19.0 and 17.5 months, respectively, met inclusion criterion. In HIV-negative and HIV-positive MSM, the probability of curing a lesion after first ECA was 85% and 75%, respectively. Over follow-up, 53% of HIV-negative and 61% of HIV-positive patients recurred. After first and second ECA, HIV-positive MSM were 1.28 times (P = 0.16) and 2.34 times (P = 0.009) more likely to recur than HIV-negative MSM. The majority of recurrence was due to development of additional lesions at untreated sites (metachronous recurrence). One patient (0.4%) developed ASCC. At last visit, 83% of HIV-negative and 69% of HIV-positive patients were HGAIN free. CONCLUSIONS:ECA is an effective treatment for HGAIN, with fewer patients progressing to ASCC than predicted with expectant management. HIV-positive patients are significantly more likely to recur than HIV-negative patients.
PMID: 22134151
ISSN: 1944-7884
CID: 3218102
