Oral Etoposide In Combination Research Articles

Successful treatment of mycosis fungoides (tumor stage) with low-dose oral etoposide in combination with local electron beam radiation therapy : Report of two cases

Successful treatment of mycosis fungoides (tumor stage) with low-dose oral etoposide in combination with local electron beam radiation therapy : Report of two cases

Phase I trial of oral etoposide in combination with radiotherapy in head and neck squamous cell carcinoma - GORTEC 2004–02

PurposeThis study sought to determine the maximum tolerated dose (MTD) of oral etoposide in combination with radiotherapy in head and neck squamous cell carcinoma (HNSCC).Patients and MethodsPhase I, multicenter, open-labelled, non-comparative and dose escalating trial. Patients with locally advanced HNSCC were enrolled onto cohorts of escalating dose of etoposide. Oral etoposide was administered on five consecutive days every week for 7 weeks (7 treatment cycles) in combination with daily radiotherapy (70 Gy /35 fractions). Two dose levels (25 mg/day and 50 mg/day) of etoposide were planned and three to six patients were to be enrolled at each level according to the potential DLTs.ResultsFourteen patients were allocated to two dose levels: 25 mg/day (3) and 50 mg/day (11). Cisplatin was contra-indicated in all the patients included. Only one patient (50 mg/day) presents a grade 4 neutropenia (DLT), no other DLTs were observed. The most frequently adverse events (AEs) were radiomucositis. Two deaths before 3 months of end of treatment were not related to treatment. Seven patients were still alive with a median follow-up of 30 months (12–58 months). Nine patients had a complete response (CR) at 3 months after the radiotherapy; Among the 9 patients, 3 patients had a local relapse; one patient with local and distant relapse.ConclusionDue to only one DLT experienced, it is possible to a dose of 50 mg/day for phase II studies, however this should be considered with caution.

Duration: escalation study of oral etoposide with carboplatin in patients with varied solid tumors

Prolonged fractionated oral administration of etoposide may present a theoretical advantage over intravenous administration of the bolus. This phase I trial was carried out to determine the recommended duration of oral etoposide in combination with a fixed dose of carboplatin. Nineteen patients with varied solid tumors, who were not candidates for standard chemotherapy, were administered an escalating duration (6, 9 or 12 consecutive days) of oral etoposide (a 25 mg capsule three times daily) combined with carboplatin AUC5 administered on day 1, by a 30 min intravenous infusion, to define the maximum tolerated dose on the basis of the acute toxicities that were reported. Etoposide was started on day 2; the cycles repeated every 28 days until disease progression or toxicity. Pharmacokinetics was carried out during the two first cycles. The maximum tolerated dose was determined to be the 12-day treatment level, with two cases of grade 4 neutropenia, grade 3 anemia and thrombocytopenia. As no severe toxicity occurred with the 9-day treatment level and in an attempt to explore an optimal combination, a new 10-day treatment plan was studied in three patients. As one patient presented dose-limiting toxicity at that level, five additional patients were included to establish the recommended regimen. Nonhematological toxicities among all patients were moderate, consisting of grade 2 nausea and asthenia. No treatment-related death occurred. Objective responses were observed in four patients and stabilization in three patients. Pharmacokinetics highlighted no interaction between etoposide and carboplatin. Fractionated oral etoposide (3×25 mg/day) for 10 days in combination with carboplatin AUC 5 presents acceptable toxicity and efficacy. The main toxicity remains hematological.

Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Phase I trial of oral etoposide in combination with celecoxib in patients with advanced malignancies

Phase I trial of oral etoposide in combination with celecoxib in patients with advanced malignancies

A Phase I Trial of Prolonged Oral Etoposide and Liposomal Doxorubicin in Ovarian, Peritoneal, and Tubal Carcinoma: A Gynecologic Oncology Group Study

Objectives. In an effort to explore second-line therapy in ovarian, peritoneal, and tubal carcinoma, a phase I trial combining prolonged oral etoposide and liposomal doxorubicin was conducted by the Gynecologic Oncology Group.Methods. Liposomal doxorubicin (20 mg/m2) was administered intravenously over 1 h followed by oral etoposide at 50 mg/m2/day beginning on day 2. In the first phase of accrual, the number of days of oral etoposide was increased until its maximum tolerated dose (MTD) was determined based on hematologic toxicity. In the second phase, etoposide was given at the MTD while the dose of liposomal doxorubicin was escalated until its maximum tolerated dose was reached based on hematologic or nonhematologic toxicity. Cycles were repeated every 28 days for a maximum of 12 courses. Dose-limiting toxicity was defined as neutropenic sepsis, grade 4 thrombocytopenia, absolute neutrophil count <1000/μl or platelets <50,000 during treatment with etoposide, or ≥grade 3 mucositis/stomatitis, palmar–plantar erythrodyesthesia, or rash.Results. Fifteen patients were accrued to the study's first phase, and 3 were accrued to the second phase. Dose-limiting hematologic toxicity occurred with 14 days of oral etoposide in combination with liposomal doxorubicin at 20 mg/m2. Efforts to escalate the dose of liposomal doxorubicin to 30 mg/m2 in combination with 12 days of oral etoposide at 50 mg/m2 resulted in dose-limiting hematologic toxicity. Five of 17 (29%; 95% CI: 13–53%) evaluable patients experienced a response.Conclusion. The regimen of oral etoposide at 50 mg/m2/day for 12 days in combination with liposomal doxorubicin at a dose of 20 mg/m2 is tolerable without supportive therapy. While this dose of oral etoposide has demonstrated activity as a single agent in ovarian cancer, liposomal doxorubicin has only been effective in ovarian cancer at higher doses. There are no immediate plans to study this combination further.

Prolonged oral etoposide in combination with intravenous cisplatin (oral EP) for non-small cell lung cancer (NSCLC)

Prolonged oral etoposide in combination with intravenous cisplatin (oral EP) for non-small cell lung cancer (NSCLC)

Phase II study of prolonged oral etoposide in combination with intravenous cisplatin in advanced non-small cell lung cancer: Miller AA, Niell HB, Griffin JP. VA Affairs Medical Center, Department of Medicine, Division Hematology/Medical Oncology, 3 North Dunlap, Memphis, TN 38163. Lung Cancer (Ireland) 1995;12:59–65

Phase II study of prolonged oral etoposide in combination with intravenous cisplatin in advanced non-small cell lung cancer: Miller AA, Niell HB, Griffin JP. VA Affairs Medical Center, Department of Medicine, Division Hematology/Medical Oncology, 3 North Dunlap, Memphis, TN 38163. Lung Cancer (Ireland) 1995;12:59–65

Phase 2 study of prolonged administration of oral etoposide in combination with weekly cisplatin in advanced non-small cell lung cancer: Robert F, Wheeler RH, Molthrop D, Bailey A, Chen S. Birmingham VA Medical Center, 700 South 19th Street, Birmingham, AL 35233. Am J Clin Oncol Cancer Clin Trials 1994;17:383–386

Phase 2 study of prolonged administration of oral etoposide in combination with weekly cisplatin in advanced non-small cell lung cancer: Robert F, Wheeler RH, Molthrop D, Bailey A, Chen S. Birmingham VA Medical Center, 700 South 19th Street, Birmingham, AL 35233. Am J Clin Oncol Cancer Clin Trials 1994;17:383–386

Phase II study of prolonged oral etoposide in combination with intravenous cisplatin in advanced non-small cell lung cancer

The objectives of the study were to evaluate the combination of cisplatin and prolonged oral etoposide for response rate, survival, and toxicity. The treatment regimen consisted of etoposide (50 mg/m 2/day) p.o. for 21 consecutive days and cisplatin (100 mg/m 2) i.v. on day 1 every 28 days for up to six courses. Patients with Stage IIIB or IV non-small cell lung cancer who had not received prior chemotherapy and had an ECOG performance status of 0–2 were eligible if they had normal bone marrow, liver and renal functions. Patients were followed weekly for toxicity including complete blood counts. The total number of patients entered in the study was 60, of whom 56 were male and four female, 40 white and 20 African Americans. Median age was 64 years (range, 39–77). Performance status 0, 1, and 2 was present in five, 39, and 16 patients, respectively. Fourteen patients had Stage IIIB and 46 Stage IV disease. A total of 142 treatment courses were administered (median 2, range 1–6). Three patients had a complete response and 19 patients had a partial response for an objective response rate of 37% (95% confidence interval, 31–43%). Median survival was 5 months (range, 1–39+). Neutropenia was the major toxicity with Grade 4 occurring in 25 patients after the first course. The following percent of patients experienced severe or life-threatening hematologic toxicity (Grade 3 and 4 combined) over all courses: leukopenia, 73%; neutropenia, 73%; anemia, 42%; and thrombocytopenia, 37%. Three patients died of neutropenic sepsis. This regimen of prolonged etoposide with cisplatin is active in advanced non-small cell lung cancer, but has substantial toxicity.

Phase 2 Study of Prolonged Administration of Oral Etoposide in Combination with Weekly Cisplatin in Advanced Non-Small Cell Lung Cancer

We administered chemotherapy consisting of a 21-day course of oral etoposide (50 mg/m2/day) and a 3-weekly dose of cisplatin (30-33 mg/m2/week) to 23 chemotherapy-naive patients with advanced non-small cell lung cancer (NSCLC). Six patients achieved a partial response (28.6%; 95% confidence interval, 11.3-52.2%), with a median response duration of 4 months and a median overall survival of 5 months. Besides alopecia, myelosuppression was the most significant drug-related toxicity. Observed side effects in 59 cycles of chemotherapy were granulocytopenia (< 1,000/microliters) in 23% of the treatment cycles, thrombocytopenia (< 75,000/microliters) in 25%, anemia (< 10 g/dl) in 64%, and nausea-vomiting (grades > or = 2) in 8%. Mild renal insufficiency (serum creatinine, 1.5-2.1 mg/dl) occurred in six patients. Three toxic deaths were observed during or immediately after cycle 1, and were related to granulocytopenia. We conclude that this regimen has modest activity in advanced NSCLC; but this therapeutic approach does not appear to produce a major improvement in the treatment of this disease. Thus, in advanced NSCLC, continued evaluation of new chemotherapeutic agents should remain the major emphasis of investigational therapy.

Clinical and pharmacological phase II study of prolonged oral etoposide in combination with intravenous cisplatin in advanced non-small cell lung cancer (NSCLC) : A.A. Miller, H.B. Niell, J.P. Griffin, E.A. Tolley. University of Tennessee, Memphis, Tennessee, USA

Clinical and pharmacological phase II study of prolonged oral etoposide in combination with intravenous cisplatin in advanced non-small cell lung cancer (NSCLC) : A.A. Miller, H.B. Niell, J.P. Griffin, E.A. Tolley. University of Tennessee, Memphis, Tennessee, USA

A randomized trial to compare intravenous and oral etoposide in combination with cisplatin for the treatment of small cell lung cancer : Johnson DH, Ruckdeschel JC, Keller JH, Lyman GH, Kallas GJ, Macdonald J et al. Division of Medical Oncology, Vanderbilt University, Nashville, TN. Cancer 1991;67:Suppl 245-9

A randomized trial to compare intravenous and oral etoposide in combination with cisplatin for the treatment of small cell lung cancer : Johnson DH, Ruckdeschel JC, Keller JH, Lyman GH, Kallas GJ, Macdonald J et al. Division of Medical Oncology, Vanderbilt University, Nashville, TN. Cancer 1991;67:Suppl 245-9

A phase I study of chronic daily dosing of oral etoposide in combination with cisplatin for patients with advanced cancer

A dose escalation study of daily oral etoposide and cisplatin was carried out on 22 patients with advanced cancer using starting doses of 20 mg/m2/d of etoposide given orally for 21 days and 80 mg/m2 of cisplatin given intravenously (IV) on day 1. A total of 40 courses were given. Myelosuppression was the major dose-limiting toxicity, with a maximum tolerated dose of 50 mg/m2/d of oral etoposide for 21 days plus 80 mg/m2 of IV cisplatin on day 1. Doses of 40 mg/m2/d of etoposide for 21 days plus 80 mg/m2 of cisplatin for 1 day in four of eight courses (50%) were associated with Grade 3 or worse leukopenia that occurred between days 18 and 26. However, no Grade 3 or worse thrombocytopenia occurred at this dose level. Nausea and vomiting occurred in most patients at each dose level but were mild and could be controlled by antiemetics. Alopecia also occurred frequently. Significant mucositis (Grade 4) occurred in one patient, but no other toxicities were observed. Four partial responses that lasted from 1.3 to 5.8+ months were observed in patients with cervical (one patient), small cell lung (one patient), and squamous cell lung cancer (two patients); one of them had been heavily pretreated with platin analogue-containing regimens. The recommended doses for Phase II studies on this schedule are 40 mg/m2/d of oral etoposide for 21 days plus 80 mg/m2 of IV cisplatin on day 1. A combination regimen on this schedule seems particularly effective in patients with etoposide-sensitive malignancies.

A randomized trial to compare intravenous and oral etoposide in combination with cisplatin for the treatment of small cell lung cancer

In a randomized multi-center study, 83 patients with small cell lung cancer were randomly assigned to treatment with cisplatin 100 mg/m2 intravenously (IV) day 1 and etoposide 120 mg/m2 IV days 1, 2, and 3 or cisplatin 100 mg/m2 IV day 1 and etoposide 120 mg/m2 IV day 1 and 240 mg/m2 orally days 2 and 3. Both regimens were repeated every 4 weeks. Prior to randomization, patients were stratified by extent of disease, performance status, and gender. A total of 41 patients were randomly assigned to the parenteral treatment only regimen, and 42 patients received cisplatin and IV/oral etoposide therapy. Both treatment arms were comparable regarding patient characteristics. Limited disease (LD) patients constituted 52% and 49% of the patient population for the oral and IV etoposide regimens, respectively. The overall complete response (CR) and partial response (PR) rate was 50% (95% confidence interval [CI] 35% to 65%) for the oral etoposide regimen and 59% (95% CI 44% to 74%) for the IV etoposide regimen (P = 0.438). For both regimens, 55% of the LD patients achieved either CR or PR. Time to progression and survival were comparable for both treatment arms. Hematologic toxicity was comparable in both treatment arms, with 80% of patients experiencing grade 3 or 4 neutropenia or thrombocytopenia. Moderate to severe anemia and weight loss were more predominant with the IV than with the oral regimen.