Susan Stalter

City of Hope National Medical Center, Duarte, California, United States

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Publications (5)57.7 Total impact

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    ABSTRACT: To determine the maximally tolerated dose, toxicity, and pharmacokinetics of i.p. gemcitabine. Patients had peritoneal carcinomatosis. Gemcitabine (40, 80, 120, or 160 mg/m(2)) was administered into the peritoneal cavity in 2 L of warmed saline on days 1, 4, 8, and 12 of a 28-day cycle. Thirty patients received 63 (median, 2; range, 0-6) courses. Tumors included ovary (14), uterus (2), colon (6), pancreas (3), and others (5). Dose-limiting toxicity included nausea, vomiting, diarrhea, dyspnea, fatal respiratory failure, and grade 3 elevation of alanine aminotransferase in three patients. Hematologic toxicity and pain were </=grade 2. Three patients had decreased or resolved ascites. Of 19 patients evaluable for response, 10 had stable disease (median, 3.5 courses) and 9 had progressive disease. The median peak peritoneal concentration was 1,116-fold (range, 456-1,886) higher than the peak plasma level. Plasma and peritoneal levels were undetectable within 8 to 12 h. At 120 mg/m(2), the median peritoneal area under the concentration versus time curve (AUC) was 82,612 ng/mL x h (range, 53,296-199,830) and the plasma AUC was 231 ng/mL x h (range, 47.6-259.5). The mean peritoneal advantage (AUC(peritoneal)/AUC(plasma)) was 847 (range, 356-1,385). I.p. administration of gemcitabine is tolerated within the tested dosage range. Technical problems with the Porta-Cath device and i.p. therapy per se may have been exacerbated by the enrollment of many patients with a variety of advanced i.p. diseases. Given the significant increase in local dose intensity and the documented activity of this drug, this agent may be an excellent candidate for i.p. therapy in optimally debulked ovarian cancer, either alone or in combination.
    No preview · Article · Feb 2007 · Clinical Cancer Research
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    ABSTRACT: We evaluated the antitumor activity of tandem cycles of high-dose chemotherapy with autologous peripheral stem cell transplantation (aPSCT) in relapsed germ cell tumors by using high-dose paclitaxel, carboplatin, etoposide, and ifosfamide. Thirty-three patients were entered, and 31 underwent protocol therapy. Paclitaxel 350 mg/m2 (5 patients) or 425 mg/m2 (26 patients) by 24-hour continuous intravenous infusion was followed by 3 daily doses of carboplatin and either etoposide (cycle 1) or ifosfamide/mesna (cycle 2). The carboplatin dose had a calculated area under the curve of 7 mg-min/mL, and the daily dose of etoposide was 20 mg/kg (cycle 1). Ifosfamide 3 g/m2/d for 3 days (with mesna uroprotection) was substituted for etoposide in cycle 2. Each cycle was supported by granulocyte colony-stimulating factor-mobilized peripheral blood stem cells. Thirty-one patients were evaluable for response, toxicity, and long-term disease control. Two patients did not undergo aPSCT because of rapid disease progression. Nineteen patients received both cycles of aPSCT, 8 progressed after cycle 1, 3 refused the second cycle, and 1 died of fungal infection during cycle 1. Twelve patients remain relapse free at a median of 67 months from the initiation of therapy. Whereas the International Germ Cell Cancer Collaborative Group category at the time of initial diagnosis did not seem to predict outcome, the patient's probability of achieving durable remission was significantly associated with the Beyer prognostic score at the time of protocol entry. Regimens containing the most active agents in relapsed nonseminomatous germ cell tumors, including high-dose paclitaxel, are well tolerated and have promising activity even in patients with poor-risk features who do not achieve durable remissions with standard therapy. The Beyer prognostic system is a valuable predictor for patients undergoing aPSCT.
    Full-text · Article · Dec 2005 · Biology of Blood and Marrow Transplantation
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    ABSTRACT: The purpose of this Phase I study was to determine the maximum tolerated dose and dose-limiting toxicities (DLTs) of i.p. docetaxel and to determine the peritoneal pharmacokinetics and pharmacological advantage of this agent. Twenty-one patients with peritoneal carcinomatosis received docetaxel administered via an implanted i.p. catheter at doses of 40, 80, 100, 125, or 156 mg/m2 every 3 weeks. DLTs on course 1 were used to define the maximum tolerated dose. Tumor types included gastric adenocarcinoma (n=7), ovarian cancer (n=4), other gastrointestinal primaries (n=3), and other cancers (n=7). Sixty cycles of i.p. docetaxel (median, 2; range, 1-11) were delivered. DLTs occurred in two patients at the 156 mg/m2 dose level; both developed an ileus, and one patient died of neutropenic sepsis. One of five evaluable patients treated with 125 mg/m2 docetaxel i.p. developed grade 4 neutropenic sepsis and stomatitis; another patient developed renal failure attributable to glomerulonephritis and grade 3 thrombocytopenia that was not judged to be dose-limiting. One of six patients receiving 100 mg/m2 D, the recommended Phase II dose, developed grade 4 neutropenia lasting <5 days. Other non-DLT treatment-related toxicities included dehydration requiring i.v. fluids, emesis, stomatitis, constipation, and abdominal pain. Best response on protocol therapy included 7 of 18 patients with stable disease for a median of 5 cycles (range, 2-11); 11 patients progressed by the first evaluation after a median of 2 cycles (range, 1-3). There were three patients inevaluable for response who received only one cycle of i.p. docetaxel (two because of patient preference and one because of adhesion formation). Pharmacokinetic evaluation revealed mean plasma areas under the curves (AUC) at 100 and 125 mg/m2 i.p. docetaxel of 3.14 and 6.33 microM.h (ranges, 1.02-5.88 and 3.97-12.70 microM. h), respectively; the mean peritoneal AUCs were 315 and 1063 microM.h (ranges, 250-373 and 239-2222 microM.h), respectively. The mean peak plasma concentrations at 100 and 125 mg/m2 i.p. docetaxel were 0.46 and 0.66 microM, and the mean peak peritoneal concentrations at those doses were 59 and 81 microM, respectively. The median and mean pharmacological advantage calculations (AUCperitoneal/AUCplasma) across all dose levels were 152 and 181, respectively (range, 18.8-367.4). The mean peritoneal 24- and 96-h concentrations were 0.9 microM (range, 0.2-1.6 microM) and <0.1 nM, respectively. The mean time that the concentration was >0.1 microM was 31.2 h (range, 27-36.5 h). i.p. docetaxel can be safely delivered at a dose of 100 mg/m2 i.p. every 3 weeks. This route of administration provides a significant peritoneal pharmacological advantage while delivering systemic concentrations consistent with the administration of standard i.v. doses.
    No preview · Article · Dec 2003 · Clinical Cancer Research
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    ABSTRACT: Tumor angiogenesis mediated by vascular endothelial growth factor (VEGF) is inhibited by the recombinant humanized (rhu) monoclonal antibody (MAb) rhuMAbVEGF, which has synergy with chemotherapy in animal models. The present study was designed to assess the safety and pharmacokinetics of weekly intravenous (IV) rhuMAbVEGF with one of three standard chemotherapy regimens. Twelve adult patients were enrolled four on each combination. rhuMAbVEGF, 3 mg/kg IV, was administered weekly for 8 weeks with (1) doxorubicin 50 mg/m(2) every 4 weeks; (2) carboplatin at area under the curve of 6 plus paclitaxel 175 mg/m(2) every 4 weeks; and (3) fluorouracil (5-FU) 500 mg/m(2) with leucovorin 20 mg/m(2) weekly, weeks 1 to 6 every 8 weeks. The median number of rhuMAbVEGF doses delivered was eight (range, four to eight doses). Grade 3 toxicities were diarrhea (one 5-FU patient), thrombocytopenia (two patients on carboplatin plus paclitaxel), and leukopenia (one patient on carboplatin plus paclitaxel). These toxicities were likely attributable to the chemotherapy component of the regimen. The mean (+/- SD) peak serum level of rhuMAbVEGF was 167 +/- 46 microg/mL, and the mean terminal half-life was 13 days. Total (free plus bound) serum VEGF levels increased from 51 +/- 39 pg/mL (day 0) to 211 +/- 112 (day 49) pg/mL. Three responding patients continued treatment with rhuMAbVEGF and chemotherapy, receiving the equivalent of 36, 20, and 40 total rhuMAbVEGF doses with no cumulative or late toxicities. rhuMAbVEGF can be safely combined with chemotherapy at doses associated with VEGF blockade and without apparent synergistic toxicity. Its contribution to the treatment of advanced solid tumors should be evaluated in randomized treatment trials.
    No preview · Article · Mar 2001 · Journal of Clinical Oncology
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    ABSTRACT: We investigated the safety and pharmacokinetics of a recombinant human monoclonal antibody to vascular endothelial growth factor (rhuMAb VEGF) in patients with cancer. Cohorts of patients with metastatic cancer having failed prior therapy entered a phase I trial of rhuMAb VEGF administered by a 90-minute intravenous infusion at doses from 0.1 to 10.0 mg/kg on days 0, 28, 35, and 42. Patients underwent pharmacokinetic sampling on day 0 and had serum samples obtained during the subsequent 28 days. Response assessment was carried out on days 49 and 72. Twenty-five patients with a median Eastern Cooperative Oncology Group performance status of 0 were accrued. There were no grade III or IV adverse events definitely related to the antibody. There were three episodes of tumor-related bleeding. Infusions of rhuMAb VEGF were well tolerated without significant toxicity. Grades I and II adverse events possibly or probably related to study drug included asthenia, headache, and nausea. Pharmacokinetics revealed a linear profile with a half-life of 21 days. There were no objective responses, though 12 patients experienced stable disease over the duration of the study. rhuMAb VEGF was safely administered without dose-limiting toxicity at doses ranging up to 10 mg/kg. Multiple doses of rhuMAb VEGF were well tolerated, and pharmacokinetic studies indicate that doses of > or = 0.3 mg/kg have a half-life similar to that of other humanized antibodies. Subsequent trials will explore rhuMAb VEGF alone and in combination chemotherapy.
    No preview · Article · Feb 2001 · Journal of Clinical Oncology