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Ischemic Colitis Associated with Paclitaxel and Carboplatin Combination.

ABSTRACT: A 62-year-old white female with a history of early-stage triple-negative breast cancer on a combination of carboplatin and paclitaxel in the adjuvant setting presented with lower gastrointestinal bleeding. She tolerated 4 cycles of dose-dense adriamycin/cyclophosphamide with no major symptoms. After 6 cycles of weekly paclitaxel in combination with carboplatin every 3 weeks, she presented with diarrhea and lower gastrointestinal bleeding. Colonosopic examination showed erythema and inflammation in the splenic flexure, descending colon, and sigmoid colon consistent with ischemic colitis. Pathology favored the same diagnosis. She was treated conservatively with intravenous fluids and bowel rest. Chemotherapy was held for 2 weeks and resumed after recovery without carboplatin. She was able to tolerate the remaining 6 cycles of paclitaxel with no recurrence of her symptoms.

SUBMITTER: Elsayed AG

PROVIDER: S-EPMC5582519 | biostudies-literature | 2017 May-Aug

REPOSITORIES: biostudies-literature

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Ischemic Colitis Associated with Paclitaxel and Carboplatin Combination.

Elsayed Ahmed Gamal AG Srivastava Roma R Pacioles Toni T Limjoco Teresa T Tirona Maria Tria MT

Case reports in oncology 20170501 2

A 62-year-old white female with a history of early-stage triple-negative breast cancer on a combination of carboplatin and paclitaxel in the adjuvant setting presented with lower gastrointestinal bleeding. She tolerated 4 cycles of dose-dense adriamycin/cyclophosphamide with no major symptoms. After 6 cycles of weekly paclitaxel in combination with carboplatin every 3 weeks, she presented with diarrhea and lower gastrointestinal bleeding. Colonosopic examination showed erythema and inflammation ...[more]

PMID: 28878651

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Project description:PURPOSE:Afatinib, an irreversible ErbB family blocker, has demonstrated preclinical antitumor activity with chemotherapy. METHODS:As part of a phase I trial in patients with advanced solid tumors (NCT00809133; 3?+?3 dose-escalation design), we determined the maximum tolerated dose (MTD) of afatinib with carboplatin (A/C) or with carboplatin plus paclitaxel (A/C/P). Starting doses: afatinib 20 mg/day, carboplatin AUC6 (A/C) with paclitaxel 175 mg/m2 (A/C/P) (chemotherapy: Day 1 of 21-day cycles). The primary objective was to determine the MTDs; safety, pharmacokinetics and antitumor activity were also evaluated. RESULTS:Thirty-eight patients received A/C (n?=?12) or A/C/P (n?=?26). No dose-limiting toxicities (DLTs) were reported with A(20 mg)/C(AUC6). One patient experienced DLT in the A(40 mg)/C(AUC6) cohort (grade 3 acneiform rash); A(40 mg)/C(AUC6) was determined as the recommended phase II dose (RP2D) for A/C. Two patients each had DLTs with A(20 mg/day)/C(AUC6)/P(175 mg/m2): fatigue, infection, diarrhea, small intestine hemorrhage, dehydration, renal impairment, neutropenic sepsis (n?=?1), mucositis (n?=?1); A(40 mg)/C(AUC5)/P(175 mg/m2): febrile neutropenia (n?=?1), mucositis, fatigue (n?=?1); and A(30 mg)/C(AUC5)/P(175 mg/m2): stomatitis (n?=?1), mucositis (n?=?1). No DLT was observed with A(20 mg)/C(AUC5)/P(175 mg/m2), determined as the RP2D for A/C/P. The most frequent drug-related adverse events were (A/C; A/C/P): rash (75%; 73%), fatigue (67%; 69%), and diarrhea (58%; 88%). Drug plasma concentrations were similar between cycles, suggesting no drug-drug interactions. Objective response rates in these heavily pretreated patients were A/C, 3/12 (25%); A/C/P, 5/26 (19%). CONCLUSIONS:Afatinib 40 mg/day (approved monotherapy dose) with carboplatin AUC6, and afatinib 20 mg/day with carboplatin AUC5 and paclitaxel 175 mg/m2 demonstrated manageable safety and antitumor activity. Afatinib?>?20 mg/day in the triple combination was not well tolerated.

Project description:Background Metformin use is associated with reduced cancer risk in epidemiological studies and has preclinical anti-cancer activity in ovarian cancer models. The primary objective of this phase I study was to determine the recommended phase II dose (RP2D) of metformin in combination with carboplatin/paclitaxel in patients with ovarian cancer. Secondary objectives were to describe safety and pharmacokinetics. Methods In this single-center trial the RP2D of metformin in combination with carboplatin area under the concentration-time curve (AUC) 6 and paclitaxel 175 mg/m2 every 3 weeks (q3w) in patients with advanced epithelial ovarian cancer was determined using a 3?+?3 escalation rule at three fixed dose levels: 500 mg three times daily (tds), 850 mg tds and 1000 mg tds. Metformin was commenced on day 3 of cycle 1 and continued until 3 weeks after the last chemotherapy administration. The RP2D was defined as the dose level at which 0 of 3 or???1 of 6 evaluable subjects experienced a metformin-related dose-limiting toxicity (DLT). Safety was assessed according to CTCAE v4.0. Plasma and serum samples for pharmacokinetic (PK) analyses were collected during treatment cycles 1 and 2. Results Fifteen patients with epithelial ovarian cancer and an indication for neo-adjuvant (n?=?5) or palliative (n?=?10) treatment were included. No DLTs were observed. Three patients discontinued study treatment during cycle 1 for other reasons than DLT. Six patients were treated at the RP2D of metformin 1000 mg tds. The most frequent low-grade toxicities were anemia, hypomagnesemia and diarrhea. Grade 3 adverse events (AEs) occurred in ten patients, most common were leucopenia (n?=?4), thrombocytopenia (n?=?3) and increased GGT (n?=?3). There were no grade 4 AEs. Metformin increased the platinum (Pt) AUC (?22%, p?=?0.013) and decreased the Pt clearance (?-28%, p?=?0.013). Metformin plasma levels were all within the therapeutic range for diabetic patients (0.1-4 mg/L). Conclusion The RP2D of metformin in combination with carboplatin and paclitaxel in advanced ovarian cancer is 1000 mg tds. This is higher than the RP2D reported for combination with targeted agents. A potential PK interaction of metformin with carboplatin was identified.

Project description:BackgroundRidaforolimus is a mammalian target of rapamycin inhibitor that has activity in solid tumors. Paclitaxel and carboplatin have broad antineoplastic activity in many cancers. This phase I trial was conducted to determine the safety profile, maximal tolerated dose, and recommended phase II dose and schedule of oral ridaforolimus combined with paclitaxel and carboplatin in patients with solid tumor cancers.MethodsEligible patients with advanced solid tumor cancers received oral 10 to 30 mg ridaforolimus daily for 5 consecutive days per week combined with intravenous paclitaxel (175 mg/m2) and carboplatin (area under the curve [AUC] 5-6 mg/mL/min) in 3-week cycles. A standard 3 + 3 design was used to escalate doses, with predefined changes to an alternate dosing schedule and/or changes in carboplatin AUC doses based on dose-limiting toxicity (DLT). Secondary information was collected regarding response and time to progression. Patients were continued on treatment if therapy was tolerated and if stable disease or better was demonstrated.ResultsThirty-one patients were consented, 28 patients were screened, and 24 patients met eligibility requirements and received treatment. Two patients were replaced for events unrelated to drug-related toxicity, resulting in 22 DLT-evaluable patients. Two grade 4 DLTs due to neutropenia were observed at dose level 1. The next cohort was changed to a predefined alternate dosing schedule (days 1-5 and 8-12). DLTs were neutropenia, sepsis, mucositis, and thrombocytopenia. The most common adverse events were neutropenia, anemia, thrombocytopenia, fatigue, alopecia, nausea, pain, and leukopenia. Twenty-four patients received a median of 4 cycles (range, 1-12). Evaluable patients for response (n = 18) demonstrated a median tumor measurement decrease of 25%. The best response in these 18 patients included 9 patients with partial response (50%), 6 with stable disease (33%), and 3 with progressive disease (17%). Thirteen of these patients received treatment for 4 or more cycles.ConclusionsTreatment with ridaforolimus combined with paclitaxel and carboplatin had no unanticipated toxicities and showed antineoplastic activity. The recommended phase II dose and schedule is ridaforolimus 30 mg (days 1-5 and 8-12) plus day 1 paclitaxel (175 mg/m2) and carboplatin (AUC 5 mg/mL/min) on a 21-day cycle.Trial registrationClinicalTrials.gov Identifier: NCT01256268 (trial registration date: December 1, 2010).

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Ischemic Colitis Associated with Paclitaxel and Carboplatin Combination.

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Ischemic Colitis Associated with Paclitaxel and Carboplatin Combination.

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