Low-dose Oral Etoposide Research Articles

7. Effect of low-dose oral etoposide on CA-125 in patients with advanced epithelial ovarian cancer

7. Effect of low-dose oral etoposide on CA-125 in patients with advanced epithelial ovarian cancer

Intermittent continuous infusion of fluorouracil, low-dose oral leucovorin and oral etoposide in advanced gastric cancer

Gastric carcinoma is considered moderately chemosensitive, but a 'standard' chemotherapy regimen has not yet been found. Encouraging results in terms of activity and tolerability have been reported with a combination of i.v. leucovorin, fluorouracil and etoposide. However, etoposide and fluorouracil have demonstrated a schedule-dependency with high activity for the former when administered orally and for the latter when administered as a continuous infusion. In order to improve clinical results, we tested the activity and feasibility of the following combination: oral L-leucovorin, 5 mg/m(2) days 1-14; oral etoposide, 50 mg/m(2) days 1-14; fluorouracil, 200 mg/m(2)/day by continuous infusion days 1-14; cycles repeated every 28 days. A total of 26 patients [male/ female, 17/9; median age, 65 years (range, 42-75); performance status, 0-2] have been enrolled and are evaluable for response and side effects. A total of 78 cycles has been delivered (median/patient, 3 cycles). Two complete remissions (8%), 11 partial remissions (42%), 4 stabilizations of disease, and 9 progressions have been observed, for an overall response rate of 50% (95% confidence interval 30-70%). Median time to disease progression was 4.5 months and median survival 9.5 months. No toxic death or grade III-IV toxicity has been observed. Mild or moderate side effects included mucositis (42%), nausea/vomiting (19%) and leukopenia (8%). In conclusion, our results indicate that the schedule is safe, well tolerated and highly effective in advanced gastric cancer.

Response of recurrent medulloblastoma to low-dose oral etoposide.

The outcome for patients with recurrent medulloblastoma has historically been poor, with most patients dying of disseminated disease. Here, we report on seven patients with recurrent medulloblastoma, most heavily pretreated with a variety of chemotherapeutic agents, including parenteral etoposide (VP-16), who showed responses to the administration of repeated courses of low-dose oral VP-16. Seven patients age 4 to 16 years were treated with VP-16 after neuroradiographic and clinical evidence of tumor progression. Six had received prior irradiation. All seven had been pretreated with a variety of chemotherapeutic agents and schedules, including parenteral VP-16. VP-16 was administered orally as repeated 21-day courses at 50 mg/m2/d with a 7-day interval between courses. Evaluation consisted of neuroradiographic and clinical examination after completion of every two courses of therapy. Complete blood cell counts were performed weekly. The major toxicity of oral VP-16 was hematologic, with two patients requiring platelet transfusions due to thrombocytopenia and two requiring RBC transfusions. All seven patients developed treatment-related neutropenia. Two patients were supported with granulocyte colony-stimulating factor (G-CSF) between courses. One patient developed infectious epididymitis after course 2 and required intravenous antibiotics; this illness was complicated by Clostridium difficile colitis. There was one episode of fever associated with neutropenia. There were no treatment-related deaths. Of seven patients assessed, six have demonstrated partial responses (PRs) and the remaining patient had stable disease (SD). This report demonstrates the activity of oral VP-16 in the treatment of a small cohort of pretreated patients with recurrent medulloblastoma. This form of administration of oral VP-16 was well tolerated and produced modest toxicity.

A Case of Extragonadal Germ Cell Tumor with Elevated Postchemotherapy HCG Successfully Treated by Resection of a Solitary Metastasis and Chronic Oral Etoposide

We report a 39 year-old man with disseminated extragonadal germ cell tumor (GCT), whose serum level of human chorionic gonadotropin (HCG) increased again after platinum-based combination chemotherapy, high-dose chemotherapy with autologous bone marrow rescue and radical adjunctive surgery. The increase in the HCG level was progressive in spite of multiple chemotherapy, and after a while, a coin lesion in the right lung was identified by chest roentgenography. The pulmonary lesion was refractory to additional chemotherapy. After a systemic survey to confirm that the lesion was solitary, video-assisted thoracoscopic wedge resection of the right lower lobe was performed. Because the resected tumor included viable tumor cells and the serum HCG level remained slightly high one month after the operation, oral low-dose etoposide was begun. In a short time, the level of the serum tumor marker decreased and remained normal during the subsequent 7 months of therapy and thereafter. The patient remains in complete remission 13 months after completion of the final therapy and 3 years after the initial diagnosis. Even if the level of a serum tumor marker is high, salvage resection can be a promising therapeutic option for operable tumors that are refractory to chemotherapy. The usefulness of chronic oral etoposide for patients with GCT should be examined by further clinical trials.

Bioavailability of 50- and 75-mg oral etoposide in lung cancer patients.

This study was designed to determine the bioavailability of etoposide capsules administered orally at doses of 50 and 75 mg. Patients with inoperable or relapsed lung cancer, who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 and adequate organ function, were eligible. A group of 17 patients were evaluable, all of whom were 75 years old or less, with an ECOG performance status of 0 or 1. The bioavailability of oral etoposide was determined by measuring the area under the etoposide plasma concentration versus time curve (AUC) on days 1, 10 and 21 during a once-daily regimen of oral administration for 21 consecutive days and comparing the value with the AUC achieved following intravenous administration 1 or 2 weeks after the last oral dose. The bioavailability of 50, 75 and 100 mg oral etoposide was determined in six, nine and two patients, respectively. The mean etoposide bioavailabilities (+/- SD) of the 50-mg and 75-mg doses were 47 +/- 11% and 59 +/- 18%, respectively, and of the 100-mg dose in two patients were 51% and 33%, respectively. There was no statistically significant difference in bioavailability between the 50-mg and 75-mg doses. The bioavailability of low-dose oral etoposide was the same as that reported in previous higher dose oral etoposide bioavailability studies and that shown on the package insert supplied by the manufacturer. Improved bioavailability of low-dose oral etoposide was therefore not observed in a population of Japanese patients.

Second-line chemotherapy with long-term low-dose oral etoposide in patients with advanced breast cancer

In a phase II study, 27 patients with metastatic breast cancer were treated with oral etoposide as second-line chemotherapy at a dose of 50 mg/m2/day for 21 days, which courses were repeated every 4 weeks. Twenty-one patients were evaluable for response, and twenty-five for toxicity. In two (10%) patients a partial response was observed with a duration of 60 and 122 weeks respectively, and seven patients (33%) showed stable disease. Gastrointestinal toxicity was usually mild, though relatively frequent. Anemia grade II and III was observed in 20% of all courses (< 10% of all measurements), and leukopenia grade III and IV was observed in 22% of all courses (< 10% of all measurements). There was one toxic death. Reviewing the literature we calculated a response rate of intravenous etoposide treatment of 8% in 276 patients with metastatic breast cancer from 7 studies (response rates ranging between 0-14%), while (chronic) oral treatment caused a response rate of 19% in 145 patients from 8 different studies (response rates ranging between 0-35%).

Inefficacy of low-dose continuous oral etoposide in non-small cell lung cancer : Blumenreich MS, Sheth SP, Miller CL, Farnsley ES, Kellihan MJ, Joseph UG et al. JG Brown Cancer Center, 529 S. Jackson Street, Louisville, KY 40292. Am J Clin Oncol Cancer Clin Trials 1994;17:163-5

Inefficacy of low-dose continuous oral etoposide in non-small cell lung cancer : Blumenreich MS, Sheth SP, Miller CL, Farnsley ES, Kellihan MJ, Joseph UG et al. JG Brown Cancer Center, 529 S. Jackson Street, Louisville, KY 40292. Am J Clin Oncol Cancer Clin Trials 1994;17:163-5

Low-dose oral etoposide in the treatment of adult T-cell leukemia

Low-dose oral etoposide in the treatment of adult T-cell leukemia

Patient compliance with prolonged low-dose oral etoposide for small cell lung cancer : Lee CR, Nicholson PW, Souhami RL, Slevin ML, Hall MR, Deshmukh AA. Department of Oncology, Uni College and Middlesex Sch of Med, 91 Riding House Street, London W1P 8BT. Br J Cancer 1993;67:630–634

Patient compliance with prolonged low-dose oral etoposide for small cell lung cancer : Lee CR, Nicholson PW, Souhami RL, Slevin ML, Hall MR, Deshmukh AA. Department of Oncology, Uni College and Middlesex Sch of Med, 91 Riding House Street, London W1P 8BT. Br J Cancer 1993;67:630–634

Low-dose oral etoposide in epithelial cancer of the ovary

To evaluate antitumour activity, toxicity, pharmacokinetics, and the pharmacodynamic relationship with neutropenia of low-dose oral etoposide (E) in patients (pts) with epithelial cancer of the ovary previously treated with cisplatin. Eighteen pts receiving 50 mg daily of oral E for 21 days every 4 weeks. CBC with differential repeated every week. E plasma levels determined by HPLC method (sensitivity limit: 0.1 microgram/ml) with evaluation during the first cycle of bioavailability and weekly 24-hour drug concentrations. Among 17 evaluable pts, 1 partial remission of 9 months. Dose-limiting neutropenia of high inter-patient variability. Mean bioavailability value of 75%, ranging from 44% to 100%. No correlation between mean 24-hour E plasma levels and ANC nadir or relative decrease of ANC during the first cycle. Low-dose oral E is ineffective as salvage treatment in epithelial cancer of the ovary. The large variability of neutropenia requires a careful hematological monitoring to avoid severe myelosuppression.

Patient compliance with prolonged low-dose oral etoposide for small cell lung cancer

Using an 'intelligent' tablet bottle which, unknown to the patient, electronically records the times of opening we have assessed the compliance of patients with prescribed oral medication. The compliance pattern of 12 patients receiving low dose etoposide for small cell lung cancer was monitored over 25 treatment periods, representing a total of 298 days. The data were expressed as overall compliance (OC), defined as the observed number of bottle openings as a percentage of the prescribed number of doses, and as two indices representing daily and hourly irregularities in the times of opening. The OC had a mean (+/- s.d.) value of 93.2% (+/- 12%) over the 25 treatment periods, and is similar to that which we have reported in a group of lymphoma patients (Lee et al., 1992). By means of a self assessed diary card we monitored the physical and mental state of the patients. Although we found significant associations between the compliance measures and some of the diary card measures, the magnitude of the observed effects would be of little practical consequence. We conclude that, in our group of patients, inadequate compliance with oral chemotherapy would not account for any significant lack of clinical response.

Extramedullary Blast Crisis of Mixed Precursor T Lymphoblastic and Myeloblastic Features in a Patient with Chronic Myelogenous Leukemia Successfully Treated with Low-dose Oral Etoposide

Extramedullary Blast Crisis of Mixed Precursor T Lymphoblastic and Myeloblastic Features in a Patient with Chronic Myelogenous Leukemia Successfully Treated with Low-dose Oral Etoposide

Application of low-dose etoposide therapy for myelodysplastic syndromes.

The therapy for myelodysplastic syndromes (MDS) and acute leukemia (AL) transformed from MDS is not well established. Etoposide (VP 16-213) at low concentrations shows differentiation-inducing activity against leukemic cells in vitro. A prior study showed that oral low-dose etoposide therapy was effective in patients with chronic myelomonocytic leukemia. We used low-dose etoposide to treat six patients with refractory anemia with excess blasts in transformation (RAEB-t) and seven patients with AL transformed from MDS. The etoposide (50 mg, 2-7 times/week) was usually administered intravenously to ensure reliable bioavailability. Of 12 assessable patients, four RAEB-t patients achieved a partial response and one AL patient achieved complete remission. The responders became transfusion-independent, and this continued for 2-9 months while etoposide therapy was continued. Three of five responders had been resistant to prior repeated low-dose cytarabine therapy. The side effects were mild and well tolerated. Heterogeneous mechanisms were surmised to explain the clinical effects of low-dose etoposide. Several aspects, including the optimal schedule of low-dose etoposide therapy, the effect of this therapy on the patients' survival, the usefulness of combination therapy with other chemotherapeutic drug(s) and/or cytokine(s), should be investigated in the future.

Low-dose oral etoposide: a new role for an old drug?

Low-dose oral etoposide: a new role for an old drug?