Vinicius Ernani1, Rahat Jahan2, Lynette M Smith3, Alissa S Marr1, Sarah E Kimbrough4, Mary E Kos4, Jolene Tijerina4, Shannon Pivovar4, Imayavaramban Lakshmanan2, Marsha Ketcham4, Sanchita Rauth2, Kavita Mallya2, Mohd W Nasser2, Maneesh Jain2, Anne Kessinger1, Surinder K Batra2, Apar Kishor Ganti5. 1. Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, United States. 2. Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, United States. 3. Department of Biostatistics, University of Nebraska Medical Center, Omaha, NE, United States. 4. Early Phase Therapeutic Clinical Trials Unit, Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, United States. 5. Department of Medicine, VA Nebraska Western Iowa Health Care System, Omaha, NE, United States; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, United States; Early Phase Therapeutic Clinical Trials Unit, Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, United States. Electronic address: aganti@unmc.edu.
Abstract
BACKGROUND: Relapsed/refractory small cell lung cancer (SCLC) has a poor prognosis, with no good options. We evaluated a novel combination of topotecan and doxorubicin, providing sequential topoisomerase I and II inhibition, in this setting. MATERIALS AND METHODS: Adult patients (>19 years) with relapsed/refractory SCLC, who had received at least one prior chemotherapy regimen were eligible. Patients received escalating doses of oral topotecan on days 1-5 of each three week cycle (maximum - 5 cycles). The dosing cohorts were: 0.85 mg/m2, 1.05 mg/m2, 1.35 mg/m2, 1.65 mg/m2 and 2.30 mg/m2. All patients received weekly doxorubicin 20 mg/m2 intravenously starting day 6 of the first cycle and continued weekly for a maximum of 15 weeks. In the absence of pre-specified dose limiting toxicities (DLT), patients were enrolled serially to escalated dose level cohorts. RESULTS: Twenty-two patients were enrolled, of which 20 were evaluable. Median age was 61 years; 74% were male and 95% were Caucasian. Hematologic side effects were the most common adverse events. There were no therapy-related Grade 5 toxicities. Incidence of DLT based on cohorts were: DL2: 1/6 (Grade 4 thrombocytopenia), DL3: 1/6 (AST elevation) and DL4: 2/4 (Grade 4 thrombocytopenia). Response rate was 20% (4/20) and disease control rate (SD + PR) was 36%. The median progression free and overall survival were 3.6 months and 6 months, respectively. CONCLUSIONS: The combination of topotecan and doxorubicin was safe and effective in relapsed/refractory SCLC. The maximum tolerated dose of oral topotecan was 1.35 mg/m2 when given concurrently with weekly doxorubicin.
BACKGROUND: Relapsed/refractory small cell lung cancer (SCLC) has a poor prognosis, with no good options. We evaluated a novel combination of topotecan and doxorubicin, providing sequential topoisomerase I and II inhibition, in this setting. MATERIALS AND METHODS: Adult patients (>19 years) with relapsed/refractory SCLC, who had received at least one prior chemotherapy regimen were eligible. Patients received escalating doses of oral topotecan on days 1-5 of each three week cycle (maximum - 5 cycles). The dosing cohorts were: 0.85 mg/m2, 1.05 mg/m2, 1.35 mg/m2, 1.65 mg/m2 and 2.30 mg/m2. All patients received weekly doxorubicin 20 mg/m2 intravenously starting day 6 of the first cycle and continued weekly for a maximum of 15 weeks. In the absence of pre-specified dose limiting toxicities (DLT), patients were enrolled serially to escalated dose level cohorts. RESULTS: Twenty-two patients were enrolled, of which 20 were evaluable. Median age was 61 years; 74% were male and 95% were Caucasian. Hematologic side effects were the most common adverse events. There were no therapy-related Grade 5 toxicities. Incidence of DLT based on cohorts were: DL2: 1/6 (Grade 4 thrombocytopenia), DL3: 1/6 (AST elevation) and DL4: 2/4 (Grade 4 thrombocytopenia). Response rate was 20% (4/20) and disease control rate (SD + PR) was 36%. The median progression free and overall survival were 3.6 months and 6 months, respectively. CONCLUSIONS: The combination of topotecan and doxorubicin was safe and effective in relapsed/refractory SCLC. The maximum tolerated dose of oral topotecan was 1.35 mg/m2 when given concurrently with weekly doxorubicin.
Authors: L A Hammond; J R Eckardt; R Ganapathi; H A Burris; G A Rodriguez; S G Eckhardt; M L Rothenberg; G R Weiss; J G Kuhn; S Hodges; D D Von Hoff; E K Rowinsky Journal: Clin Cancer Res Date: 1998-06 Impact factor: 12.531
Authors: M Valdivieso; M A Burgess; M S Ewer; B Mackay; S Wallace; R S Benjamin; M K Ali; G P Bodey; E J Freireich Journal: J Clin Oncol Date: 1984-03 Impact factor: 44.544
Authors: Daniel Morgensztern; Benjamin Besse; Laurent Greillier; Rafael Santana-Davila; Neal Ready; Christine L Hann; Bonnie S Glisson; Anna F Farago; Afshin Dowlati; Charles M Rudin; Sylvestre Le Moulec; Satwant Lally; Sreeni Yalamanchili; Jürgen Wolf; Ramaswamy Govindan; David P Carbone Journal: Clin Cancer Res Date: 2019-09-10 Impact factor: 12.531
Authors: A W Tolcher; J A O'Shaughnessy; R B Weiss; J Zujewski; R C Myhand; E Schneider; F Hakim; R Gress; B Goldspiel; M H Noone; L R Brewster; M R Gossard; K H Cowan Journal: Clin Cancer Res Date: 1997-05 Impact factor: 12.531