E Rosvold

Fox Chase Cancer Center, Philadelphia, PA, United States

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Publications (6)12.96 Total impact

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    ABSTRACT: Phase I study to determine the maximally tolerated dose (MTD) of cisplatin (cDDP), paclitaxel (P), and concurrent split course hyperfractionated (BID) RT in advanced squamous cell carcinoma of the head and neck (SCCHN) and other upper aerodigestive tumors. Eligibility stipulated ECOG performance status 0-2 and either Tx-naïve, locally advanced, or locally recurrent, previously radiated, surgically unresectable upper aerodigestive cancer. Metastases were permitted if disease was predominantly locoregional. RT-naïve patients received 150 cGy bid x 5 d Q 2 wks x 4. Previously radiated patients received 150 cGy bid x 5, wk 1; then 120 cGy bid x 5 Q 2 wk x 3 (later increased to 150 cGy BID for the entire treatment). Treatment fields included recurrent tumor only with 2 cm margins. Whenever possible, conventional and 3-D conformal techniques were used. Elective nodal radiation was not administered. Starting doses of cDDP and P were 12 mg/m2/d x 5 and 15 mg/m2/d x 5, respectively, Q 2 wk x 4, each given on RT days only. At dose level 2, cDDP was increased to 15 mg/m2/d x 5. At dose level 3, P was increased to 20 mg/m2/d x 5. Granulocyte colony stimulating factor (G-CSF) days 6-12 (off treatment week) was added if cumulative neutropenia precipitated treatment delays. Results: Thirty-one patients (21 men, 10 women) were treated. Eight had received prior chemotherapy, 27 prior RT. At dose level three, regular treatment delays of >or=1 week due to slow neutrophil recovery occurred. Addition of G-CSF (dose level 3b) reduced treatment delays from 100 percent to 28 percent and decreased the incidence of Grade >or=2 neutropenia and mucositis. Six of 7 patients at this dose level completed all 4 cycles of treatment and all received full dose RT (60 Gy). No other dose-limiting toxicities occurred. Of 22 assessable patients with locally recurrent SCCHN, 12 (55 percent) responded. Median time to progression in this group was 6 months, with median and one-year survival of 9.5 mos and 41 percent, respectively. Concurrent daily cisplatin/paclitaxel and split course hyperfractionated RT (60 Gy) is feasible in previously radiated patients. G-CSF, administered between each cycle, reduces the incidence of treatment delays. Activity is promising and toxicity acceptable.
    Cancer Investigation 04/2006; 24(2):164-73. · 2.24 Impact Factor
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    ABSTRACT: The paclitaxel/carboplatin combination has demonstrated promising activity in metastatic non-small-cell lung cancer (NSCLC); therefore, we mounted an exploratory study of these agents with thoracic radiation (TRT) in locally advanced NSCLC. Eligibility stipulated a Karnofsky performance status >or= 70%, weight loss <or= 5%, and primarily stage IIIB or bulky IIIA NSCLC. Induction chemotherapy (CT), 2 cycles of paclitaxel 175-225 mg/m2 over 3 hours and carboplatin (targeted area under the curve [AUC] of 7.5), was administered on days 1 and 22. Granulocyte colony-stimulating factor (G-CSF) 5 microg/kg was given on days 2-15 and 23-36 to all patients; half were randomized to priming G-CSF every day x 5 prior to day 1 of induction therapy. On day 43, TRT (60-63 Gy/30-34 fx) was initiated. At dose level 1, only Fox Chase Cancer Center patients received carboplatin (initial target AUC 3.75) and paclitaxel (67.5 mg/m2 over 3 hours) days 43 and 64. In the absence of dose-limiting toxicity, phase I dose escalation in 3-patient cohorts was scheduled to proceed to a maximum carboplatin AUC 7.5 and paclitaxel dose of 210 mg/m2. To date, 53 patients have received induction therapy; 4 are too early to evaluate. The portion of the study evaluating G-CSF priming revealed no myeloprotective effect, likely due to a lack of myelosuppressive toxicity with the conventionally dosed cohort. Twenty-two patients have received concurrent TRT/CT. In sequential cohorts, the chemotherapy doses on days 43 and 64 have been escalated (to paclitaxel 175 mg/m2 and carboplatin AUC 5) with 1 episode each of grade 4 granulocytopenia and grade 3 anemia. The occurrence of grade >or= 2 esophagitis has corresponded to length (> 16 cm) of esophagus in the radiation treatment field (Fisher's exact test, P = 0.006). The partial response rate to induction therapy was 40% and to the combined modality therapy was 60%. The median survival for all 49 patients is 15.3 months, with a median disease-free survival (DFS) of 7.8 months. In the subset of 22 patients treated on the phase I portion of the study, the median survival and DFS were 18.5 months and 13.5 months, respectively. Induction therapy with paclitaxel and carboplatin followed by concurrent chemoradiotherapy with the same agents is an active and well-tolerated treatment approach in locally advanced NSCLC. To date, paclitaxel 175 mg/m2 plus carboplatin AUC 5 administered at 3-week intervals for 2 cycles is safe in combination with TRT.
    Clinical Lung Cancer 12/2001; 3(2):125-32; discussion 133. · 2.04 Impact Factor
  • Lung Cancer. 01/2000; 29(1):33-33.
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    ABSTRACT: We previously reported a 62% response rate and 54% 1-year survival rate for paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) administered by 24-hour infusion in combination with fixed-dose carboplatin to treat patients with advanced non-small cell lung cancer (NSCLC). Myelosuppression proved dose limiting, but was substantially reduced by the routine use of granulocyte colony-stimulating factor during the second and subsequent cycles. Activity for paclitaxel 135 mg/m2 and 200 mg/m2 by 1-hour infusion every 3 weeks in patients with NSCLC, with minimal myelosuppression and the suggestion of a dose-response relationship, has been reported. In November 1994, we initiated a phase II trial in patients with advanced, measurable, chemotherapy-naive NSCLC using paclitaxel 175 mg/m2 given in 1 hour, and carboplatin dosed to a fixed target area under the concentration-time curve of 7.5 every 3 weeks. In the absence of grade 4 myelosuppression, paclitaxel was escalated on an intrapatient basis by 35 mg/m2 per cycle to a maximum dose of 280 mg/m2 by cycle 4. Granulocyte colony-stimulating factor was not routinely used. Of the 57 patients accrued, 44 (81%) are Eastern Cooperative Oncology Group performance status 1. The median patient age is 64 years. To date, 54 patients are fully evaluable for toxicity. In the first 20 evaluable patients accrued (cohort A), myelosuppression was tolerable, but cumulative peripheral sensory neuropathy proved dose limiting: grade > or = 1 in 15 (75%) patients and grade 3 in six (30%), generally occurring at paclitaxel doses > or = 215 mg/m2 and obligating at least three patients to be removed from study despite absence of disease progression. The protocol was consequently revised. The starting dose of paclitaxel was reduced to 135 mg/m2 with intrapatient dose escalations of 40 mg/m2 per cycle, to a maximum paclitaxel dose of 215 mg/m2, recapitulating the original dosing schema used in Fox Chase Cancer Center study 93-024. For the 35 patients enrolled in the second cohort (cohort B), treatment has been better tolerated. Of 21 evaluable patients, 13 (62%) have experienced peripheral sensory neuropathy, grade 3 in only one (5%) patient. Myelosuppression also has been less pronounced, with 44% grade 4 granulocytopenia and 38% grade > or =3 thrombocytopenia in cohort B compared with 70% and 50%, respectively, in cohort A. Of the first 22 patients accrued to cohort A, 12 (55%) had major objective responses. Median event-free survival is 24 weeks and median survival is 47 weeks. Of the 35 evaluable patients in cohort B, nine (26%) have had major objective responses. Median event-free survival is 22 weeks. It is too early to report median survival. Paclitaxel given by 1-hour infusion in combination with carboplatin at a fixed target area under the concentration-time curve of 7.5, although active in advanced NSCLC, is associated with problems that compromise its efficacy. Higher dose levels yield intolerable toxicity, evidenced by the incidence of neurotoxicity (rather than myelosuppression) that was dose and protocol limiting at paclitaxel doses exceeding 215 mg/m2. Lower doses, while more tolerable, appear to be associated with lower response rates.
    Seminars in Oncology 08/1997; 24(4 Suppl 12):S12-81-S12-88. · 4.33 Impact Factor
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    ABSTRACT: Phosphonacetyl-L-aspartate (PALA), in inhibitor of aspartate transcarbamylase that depletes uridine nucleotide pools, selectively potentiates the antitumor activity of 5-fluorouracil (5-FU) in preclinical models. Due to the promising results we obtained using PALA/5-FU in colorectal cancer, we performed a phase II trial in patients presenting with advanced pancreatic cancer. PALA was given intravenously at 250 mg/m2 on day 1, followed 24 h later by 2,600 mg/m2 5-FU given by 24-h infusion. Treatments were repeated weekly. A total of 41 patients who had not previously undergone chemotherapy were entered in the trial; of these, 35 were evaluable for response. Toxicity was generally mild to moderate; neurotoxicity (13/35) and diarrhea (8/35) predominated. Among the 35 patients, 1 achieved a complete response and 4, a partial remission, for an overall response rate of 14%. The median survival was 5.1 months. Pretreatment with PALA alone was not sufficient to enhance the activity of 5-FU in pancreatic cancer.
    Cancer Chemotherapy and Pharmacology 02/1992; 29(4):305-8. · 2.80 Impact Factor
  • C J Langer, E Rosvold
    Current Problems in Cancer 20(4):217-79. · 1.56 Impact Factor