Current Issue : April - June Volume : 2016 Issue Number : 2 Articles : 4 Articles
Background\nWe have harnessed a novel biological system, the bacterial minicell, to deliver cancer therapeutics\nto cancer cells. Preclinical studies showed that epidermal growth factor receptor\n(EGFR)-targeted, paclitaxel-loaded minicells (EGFRminicellsPac) have antitumor effects in\nxenograft models. To examine the safety of the minicell delivery system, we initiated a firsttime-\nin-human, open-label, phase I clinical study of EGFRminicellsPac in patients with\nadvanced solid tumors.\nMethodology\nPatients received 5 weekly infusions followed by a treatment free week. Seven dose levels\n(1x108, 1x109, 3x109, 1x1010, 1.5x1010, 2x1010, 5x1010) were evaluated using a 3+3 doseescalation\ndesign. Primary objectives were safety, tolerability and determination of the maximum\ntolerated dose. Secondary objectives were assessment of immune/inflammatory\nresponses and antitumor activity.\nPrincipal Findings\nTwenty eight patients were enrolled, 22 patients completed at least one cycle of EGFR mini cells Pac;\n6 patients did not complete a cycle due to rapidly progressive disease. A total of\n236 doses was delivered over 42 cycles, with a maximum of 45 doses administered to a single\npatient. Most common treatment-related adverse events were rigors and pyrexia. No\ndeaths resulted from treatment-related adverse events and the maximum tolerated dose\nwas defined as 1x1010 EGFR mini cells Pac. Surprisingly, only a mild self-limiting elevation in the inflammatory cytokines IL-6, IL-8 and TNF�± and anti-inflammatory IL-10 was observed.\nAnti-LPS antibody titers peaked by dose 3 and were maintained at that level despite repeat\ndosing with the bacterially derived minicells. Ten patients (45%; n = 22) achieved stable disease\nas their best response.\nConclusions/Significance\nThis is the first study in humans of a novel biological system that can provide targeted delivery\nof a range of chemotherapeutic drugs to solid tumor cells. Bispecific antibody-targeted\nminicells, packaged with the chemotherapeutic paclitaxel, were shown to be safe in patients\nwith advanced solid tumors with modest clinical efficacy observed. Further study in Phase II\ntrials is planned....
Purpose: To report institutional outcomes for the use of interstitial\nbrachytherapy for locally advanced cervical cancer.\nMethods and Materials: Retrospective analysis was performed\non patients treated for cervical cancer at the Ohio State University\nWexner Medical Center from 2000 to 2014. A total of 525 patients\nwere identified and 52 of these patients received interstitial\nbrachytherapy and were included in the analysis. All patients\nreceived external beam radiation. All patients were treated with\nlow-dose-rate interstitial brachytherapy, except for one patient who\nwas treated with high-dose-rate interstitial brachytherapy. Actuarial\nestimates of disease free survival, locoregional failure free survival\n(LRFFS), distant metastasis free survival, and overall survival were\ncalculated by Kaplan-Meier.\nResults: At a median OS of 22.1 months for all 52 patients treated\nwith interstitial brachytherapy, LRFFS was 70% at 1 year, 67% at 2\nyears, and 61% at 3 years. Disease free survival at 1, 2, and 3 years\nwere 61%, 52%, and 45%, respectively. Distant metastasis free\nsurvival was 81%, 69%, and 65% at 1, 2, and 3 years, respectively.\nOverall survival was 67% at 1 year, 47% at 2 years, and 30% at 3\nyears. The grade 3 toxicity rate was 9.6% but no grade 4 or higher\ntoxicity occurred.\nConclusion: Interstitial brachytherapy provides good local control\nfor patients with locally advanced cervical cancer with acceptable\ntoxicity. However, local and distant failures are still occurring\ndespite this treatment....
Background Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel technique of intraperitoneal chemotherapy.\nFirst results obtained with PIPAC in patients with advanced peritoneal metastasis (PM) from gastric cancer\n(GC) are presented.\nMethods Retrospective analysis: Sixty PIPAC were applied in 24 consecutive patients with PM from GC. 67 % patients\nhad previous surgery, and 79 % previous platinum-based systemic chemotherapy. Mean Peritoneal Carcinomatosis Index\n(PCI) of 16Ã?±10 and 18/24 patients had signet-ring GC. Cisplatin 7.5 mg/m2 and doxorubicin 1.5 mg/m2 were given for\n30 min at 37 Ã?°C and 12 mmHg at 6 week intervals. Outcome criteria were survival, adverse events, and histological\ntumor response.\nResults Median follow-up was 248 days (range 105ââ?¬â??748), and median survival time was 15.4 months. Seventeen patients had\nrepeated PIPAC, and objective tumor response was observed in 12 (12/24=50 %): no vital tumor cells=6, major pathological resp minor resp Postoperative adverse events>CTCAE 2 were observed in 9 patients (9/24, 37.5 %). In 3/17\npatients, a later PIPAC could not be performed due to non-access. Two patients (ECOG 3 and 4) died in the hospital due to disease\nprogression.\nConclusion PIPAC with low-dose cisplatin and doxorubicin was safe and induced objective tumor regression in selected patients\nwith PM from recurrent, platinum-resistant GC. First survival data are encouraging and justify further clinical studies in this\nindication....
The skin offers an accessible and convenient site for the administration of\nmedications. To this end, the field of transdermal drug delivery, aimed at developing safe\nand efficacious means of delivering medications across the skin, has in the past and continues\nto garner much time and investment with the continuous advancement of new and innovative\napproaches. This review details the progress and current status of the transdermal drug\ndelivery field and describes numerous pharmaceutical developments which have been\nemployed to overcome limitations associated with skin delivery systems. Advantages and\ndisadvantages of the various approaches are detailed, commercially marketed products are\nhighlighted and particular attention is paid to the emerging field of microneedle technologies....
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