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PubMed1984

Phase II study of PALA, amsacrine, teniposide, and zinostatin in small cell lung carcinoma (EST 2579).

Eighty-two patients with small cell lung carcinoma refractory to standard chemotherapy were entered in this phase II randomized study of PALA, amsacrine, teniposide, and zinostatin. Of the 66 evaluable patients, one partial response occurred among 17 patients treated with teniposide and no responses occurred with the other drugs. Two patients each treated with amsacrine and teniposide experienced life-threatening hematologic toxic effects and one patient treated with zinostatin died of thrombocytopenic pulmonary hemorrhage. The overall median patient survival was 9.6 weeks. Weight loss greater than or equal to 5% prior to therapy, extensive disease, and a nonambulatory status were associated with poor survival.

Aminoacridines↗
PubMed1984

Teniposide (VM26) disposition in children with leukemia.

The clinical pharmacokinetics of teniposide (VM-26, NSC 122819) has been studied in 21 children (median age, 4.7 years) with acute lymphocytic leukemia. Teniposide was administered at a dosage of 165 mg/sq m as a 30- to 60-min i.v. infusion. Patients were studied either on the first or second dosage of the drug. Plasma samples were assayed for teniposide and metabolites by high-performance liquid chromatography with electro-chemical detection. Both compartmental and noncompartmental pharmacokinetic analyses were performed. Systemic clearance and apparent volume of distribution of steady state averaged 13.82 +/- 6.0 ml/min/sq m (S.D.) and 7.9 +/- 4.0 liter/sq m, respectively. Univariate and multivariate stepwise regression analyses were used to construct mathematical models to describe the relationships between certain patient-specific demographic and laboratory values and the pharmacokinetic parameters, systemic clearance, elimination rate constant, and area under the concentration-time curve. A significant relationship between serum alkaline phosphatase and systemic clearance, elimination rate constant, and area under the concentration-time curve was found, suggesting that liver function influences the disposition of this anticancer drug in humans.

Child↗
PubMed1997

Ether lipids enhance the cytotoxic effect of teniposide and paclitaxel in liposomes against leukaemic cells in culture.

This study investigated the relevance of combining lipophilic anti-cancer drugs intercalated into the phospholipid bilayer of liposomes. The cytotoxic interaction of two ether lipids, octadecylphosphocholine and ET-18-OCH3, and the chemotherapeutic drugs teniposide and paclitaxel on cancer cells in vitro was evaluated by use of a combined tetrazolium/formazan-labelled thymidine assay. Summation was calculated by the fractional product method. Enhanced cytotoxic activity was found with combinations of the ether lipids with both teniposide and paclitaxel against leukaemic cells. Combination of teniposide and paclitaxel showed antagonism. The benefit of the liposomal formulation form for the ether lipids was supported by the fact that their haemolytic activity was much reduced when they were incorporated into liposomes.

Antineoplastic Agents, Phytogenic↗
PubMed1996

Tandem high-dose chemotherapy with ifosfamide, carboplatin, and teniposide with autologous bone marrow transplantation for the treatment of poor prognosis common epithelial ovarian carcinoma.

BACKGROUND: A phase I or II trial was conducted to assess the toxicity and the efficacy of a tandem high dose chemotherapy combining ifosfamide, carboplatin, and teniposide in patients with poor prognosis ovarian carcinoma. METHODS: Thirty-seven patients were scheduled to receive tandem high dose therapy combining ifosfamide 7500 to 11250 mg/m2, carboplatin 875 ot 1000 mg/m2 and teniposide 750 to 1000 mg/m2, followed by autologous bone marrow transplantation (ABMT). Eight patients were refractory to the platin-based regimen, 7 were treated in chemosensitive relapse, and 22 in partial or complete response (PR/CR) were treated. Sixty-six cycles were administered. Sixteen patients were evaluated for response. RESULTS: The overall response rate was 56% (CR rate: 12%). Toxic effects consisted of mainly renal toxicity, esophagitis, and enterocolitis. Three patients died of therapy-related complications. Since the time of ABMT, the median overall survival (OS) duration of the whole population was 18 months and the survival rate was 14% at 60 months. For the 22 patients treated after PR or CR, the median OS duration was 24 months and the survival rate was 32% at 60 months. Tandem high dose therapy with ABMT was unable to circumvent resistance to conventional chemotherapy or to prolong the duration of survival for patients treated in chemosensitive relapse. For patients treated after CR or PR, the survival results were similar to that achieved with conventional therapy. CONCLUSIONS: Prospective, randomized studies, including patients only after CR or with minimal residual disease, are urgently required to evaluate the activity of high dose therapy in the treatment of advanced ovarian carcinoma.

Adult↗
PubMed1998

Carboplatin and teniposide concurrent with radiotherapy in patients with glioblastoma multiforme: a phase II study.

BACKGROUND: The outcome after treatment for glioblastoma remains poor. Therefore, the authors evaluated the long term efficacy and toxicity of treatment with radiotherapy and concurrent carboplatin plus teniposide followed by three cycles of carmustine in patients who underwent resection for glioblastoma. METHODS: Fifty-six newly diagnosed patients with glioblastoma underwent radiotherapy (1.8-2 gray [Gy]/day, 5 days a week using limited fields up to 60 Gy), and concurrent chemotherapy with carboplatin (350 mg/m2) on Days 1, 22, and 43, and teniposide (50 mg/m2) on Days 1, 2, 3, 22, 23, 24, 43, 44, and 45. Four weeks after the end of radiotherapy, patients were given carmustine (200 mg/m2) every 8 weeks for 3 cycles. Treatment then was suspended, but if disease progression was found, treatment was resumed using different drugs. RESULTS: All 56 patients were evaluated for time to progression (TTP) and median survival time (MST). The TTP was 7.5 months and the MST was 12.5 months. Toxicity manifested as thrombocytopenia and in most cases was acceptable. Four patients (7.1%) had radiation necrosis at 2, 2, 7, and 9 months, respectively, from the end of radiotherapy. CONCLUSIONS: The results obtained in the current study with concurrent radiochemotherapy in patients with glioblastoma are comparable to the best results reported using radiotherapy alone followed by chemotherapy with nitrosoureas.

Adult↗
PubMed1982

Normal infant after combination chemotherapy including teniposide for Burkitt's lymphoma in pregnancy.

A 32-year-old woman was treated for Burkitt's lymphoma diagnosed during the 22nd week of pregnancy. Chemotherapy consisting of doxorubicin (Adriamycin), vincristine, teniposide (VM-26), cyclophosphamide, and prednisolone (AVTEP) was given each 2.5 to 3 weeks from the time of the diagnosis until delivery in the 37th week. Bleomycin and intrathecal methotrexate were also given from the 35th week. The infant was born after an assisted vaginal delivery and was fully developed and normal in all respects. This paper confirms prior reports that cytotoxic chemotherapy may safely be given during the second and third trimesters of pregnancy without adverse effects on the fetus. To our knowledge it is the first report of the use of teniposide, a new podophyllin derivative, during pregnancy.

Adult↗
PubMed1985

Pharmacokinetics of teniposide (VM 26) after IV administration in serum and malignant ascites of patients with ovarian carcinoma.

Nine patients with ovarian carcinoma and malignant ascites treated with IV teniposide chemotherapy (30 mg/m2/30 min) entered this study. Plasma and peritoneal fluid levels were measured by an HPLC method with electrochemical detection. Plasma decay kinetics followed a triexponential function. A high variability of drug diffusion in ascites was noticed. Peak concentrations in ascites ranged from 1.6% to 20.5% of serum peak concentration. The concentration in peritoneal fluid reached a maximum level 6 h after the infusion ended. Teniposide was less slowly eliminated from ascites than from serum. The exposure of the inflammatory peritoneal fluid to the drug expressed by area under the concentration-time curve (AUC) was also subject to significant interindividual variation, ranging from 223 to 2332 micrograms/ml X min. However, the peritoneal AUC was correlated with serum AUC and with the systemic clearance of the drug. A significant relationship between gamma glutamyltranspeptidase and both systemic clearance and either the serum or the peritoneal AUC was found, suggesting that liver plays a role in drug disposition.

Aged↗
PubMed1987

The effect of the two epipodophyllotoxin derivatives etoposide (VP-16) and teniposide (VM-26) on cell lines established from patients with small cell carcinoma of the lung.

To determine whether there is any difference between the two epipodophyllotoxin derivatives etoposide and teniposide in their therapeutic effect in small cell carcinoma of the lung (SCCL), they were compared against five human SCCL cell lines in vitro. When the two were compared at equimolar concentrations teniposide was found to be 8-10 times more potent than etoposide, both with 1-h incubation and with continuous incubation in a clonogenic assay and in inducing cell cycle perturbations monitored by flow cytometry. Published pharmacokinetic data suggest that this potency difference is not accompanied by an equivalent increase in toxicity. The concentrations used for the 1-h incubation were about 100-fold the concentrations used in the experiments with continuous incubation to obtain the same degree of cell kill for both drugs. This suggests that they should be given according to a continuous rather than an intermittent schedule.

Animals↗
PubMed1991

Phase II study of teniposide in adenocarcinoma of the lung.

A total of 26 evaluable patients with previously untreated, non-resectable adenocarcinoma of the lung were given 80 mg/m2 i.v. teniposide daily for 5 days every 3 weeks. Three partial responses (11%) were obtained that lasted for 12, 11 and 32 weeks, respectively. Leucopenia was the dose-limiting side effect, with WBC counts of less than 2 x 10(9)/l being observed in 42% of patients, resulting in one septic death. At the dose and schedule used in the present study, teniposide showed only limited activity in adenocarcinoma of the lung.

Adenocarcinoma↗
PubMed1991

Mitomycin C, teniposide, and cisplatin combination chemotherapy for advanced non-small-cell carcinoma of the lung.

A total of 45 patients with advanced non-small-cell lung carcinoma were treated with a combination of cisplatin, teniposide, and mitomycin C. Most subjects exhibited good prognostic factors (performance status, 0-1; minimal weight loss; locoregional disease). Toxicity consisted mainly of myelosuppression and nausea and vomiting. Four patients died of sepsis due to chemotherapy-induced leukopenia. The response rate was 39.5%, with no complete responses being observed; the median duration of partial responses was 231 days and median survival was 243 days. Although the response rate and durations of both response and survival were comparable with those obtained using other cisplating-containing regimens, myelotoxicity was rather pronounced in the present study. Further studies of teniposide in this type of combination are not warranted.

Adult↗
PubMed1988

Etoposide and teniposide. Bioanalysis, metabolism and clinical pharmacokinetics.

Etoposide (VP 16-213) and teniposide (VM 26) are semisynthetic epipodophyllotoxin derivatives active against a variety of tumours. The clinical efficacy has led to an increasing interest in these compounds. This review presents information on the mechanism of action, biochemical pharmacology, bioanalysis, metabolism and pharmacokinetics of etoposide and teniposide.

Etoposide↗
PubMed1995

Influence of teniposide on platelet functions in vitro.

Teniposide added to citrated platelet-rich plasma reduced platelet aggregation induced by collagen, but did not interfere with ADP-induced aggregation. The availability of platelet factor 3 was decreased irrespective of inducer. Reptilase clot retraction induced by ADP or collagen was reduced. Teniposide did not interfere with platelet adhesion to glass. It did not release lactic dehydrogenase from the cytoplasm of platelets. Coagulation factors were not affected.

Adenosine Diphosphate↗
PubMed1990

Teniposide in recurrent or advanced cervical carcinoma: a phase II trial in patients not previously treated with cytotoxic therapy.

Thirty-two patients with advanced or recurrent cervical cancer were entered into this study of single-agent teniposide as first-line chemotherapy at a dose of 100 mg/m2 intravenously on Days 1-3 every 3 weeks. Of these patients, 7 (22%) had a partial response to therapy; no patient had a complete response. Median time to treatment failure was 13 weeks [95% confidence limits (CL): 10-21 weeks] and median survival was 28 weeks (95% CL: 14-43 weeks). Toxicity was moderate. Leukopenia and thrombocytopenia (WHO grade 3 or 4) was noted in 9 patients and 1 patient, respectively. Nausea and vomiting were mild. Seventy-five percent had alopecia requiring a wig. There were no treatment-related deaths. This study indicates that teniposide has some, although limited, activity in cervical cancer.

Adult↗
PubMed1987

Teniposide (VM-26) in patients with advanced refractory ovarian cancer: a phase II study of the Netherlands Joint Study Group for Ovarian Cancer.

In 23 evaluable patients with advanced ovarian epithelial cancer refractory to combination therapy with cisplatin and an alkylating agent, teniposide (VM-26) was administered as a short-term i.v. infusion at a dose of 100 mg/m2 on days 1 and 2, every 3 weeks. Toxicity was moderate and comparable to the pattern known from other studies. No objective response has been observed, showing that teniposide is not active as second-line therapy in this disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Phase II study of teniposide in patients with AIDS-related Kaposi's sarcoma.

Antitumour activity of cytotoxic agents, evaluated in patients with AIDS-related Kaposi's sarcoma (KS), is about 30-80%. However, responses are mostly partial and short. Experience with etoposide is similar. Teniposide has a longer elimination half-life and superior antitumour activity compared with etoposide in some experimental models. Thus a phase II trial was done in 25 patients with AIDS-related KS. Teniposide was given by 60-min infusion at 360 mg/m2 every 3 weeks. 10 (40%) showed a partial response, median duration of 9 (6-20) weeks. The main side-effects were leukopenia, thrombocytopenia, nausea and vomiting, alopecia and mucositis.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Comparative study on the determination of the anti-neoplastic drug teniposide in plasma using micellar liquid chromatography and surfactant-mediated plasma clean-up.

The potential of micellar liquid chromatography and of an on-line surfactant-mediated sample cleanup, which involves column-switching prior to conventional reversed-phase high-performance liquid chromatography, has been evaluated for the determination of the anti-neoplastic drug teniposide in plasma by using electrochemical detection. A major advantage of surfactant-mediated techniques is that they allow fully automated processing of plasma samples, because protein precipitation is prevented by the addition of the surfactant sodium dodecylsulphate. With the automated column-switching technique, a degree of sample enrichment and of selectivity can be attained, which is similar to that for the conventional procedure which, however, involves a labour-intensive off-line isolation of teniposide, using liquid-liquid extraction prior to chromatography. An inherent drawback of automated micellar liquid chromatography is that no sample clean-up or preconcentration can be carried out, which results in only a moderate detection limit and selectivity. The linearity, reproducibility and recovery of the surfactant-mediated techniques are similar to those of the conventional procedure. Based on the presented results, it was concluded that the surfactant-mediated column-switching technique is a highly attractive sample enrichment technique with respect to simplicity, speed and cost.

Chromatography, High Pressure Liquid↗
PubMed1992

Teniposide as single drug therapy for elderly patients affected by small cell lung cancer.

From January 1987 to December 1990, 26/105 previously untreated patients affected by small cell lung cancer (SCLC), not suitable for intensive SCLC treatment since 19 of them were older than 70 years and 7 suffered from severe chronic diseases, received induction therapy consisting of teniposide alone, 60 mg/m2 on days 1-5, every 3 weeks until disease progression. After a minimum of two courses, 24 patients were evaluable for response: 13 with limited disease (LD) and 11 with extensive disease (ED) (2 patients were unevaluable: 1 early death and 1 protocol violation). Response rate, by disease stage, was: in the 13 LD, 1 complete response (CR), 8 partial responses (PR), 2 minor responses and 2 failures; in the 11 ED, 1 CR, 4 PR and 6 failures. The overall response rate was 58% (14/24) (95% confidence limits = 38-78%), comprising 8% CR and 50% PR. Median duration of response was 7 months (range 2-32). Median overall duration of survival was 9 months (range 1.5-36+). Toxicity was haematological WHO grade III in 13% of courses delivered, whereas no further important side-effects were recorded, excluding alopecia, which was common. Teniposide used alone appeared a safe and effective palliative treatment for poor-risk patients; the major limitation was the low CR rate.

Aged↗
PubMed1999

Teniposide (VM-26) treatment enhances the radiation-induced micronuclei in the bone marrow of mouse.

The effect of Teniposide (VM-26) pretreatment was studied on the micronuclei induction in the bone marrow of mice exposed to 0, 0.5, 1, 2 and 3 Gy of gamma radiation at 12, 24 and 36 h post-irradiation. Administration of 0.05 mg/kg body weight of VM-26 to mice before irradiation resulted in the significant enhancement of micronucleated polychromatic erythrocytes (MPCE) at 12, 24 and 36 h post-irradiation. Highest elevation in the frequency of MPCE was observed in VM-26+irradiation group after exposure to 0.5 Gy when compared to concurrent DDW+irradiation group. This increase was two fold higher in VM-26+irradiation group at 12 and 24 h, while it was 3 fold higher at 36 h post-irradiation compared to DDW+irradiation group. The peak frequency of MPCE was observed at 24 h post-irradiation in both groups, which declined thereafter. The frequency of micronucleated normochromatic erythrocytes (MNCE) increased in a dose dependent manner in both DDW+irradiation and VM-26+irradiation groups. However, the frequency of MNCE was significantly higher in the latter when compared to the former group. The frequency of MNCE exhibited a continuous elevation up to 36 h post-irradiation in both DDW+irradiation and VM-26+irradiation groups. Treatment of mice with teniposide before irradiation resulted in a significant decline in the PCE/NCE ratio compared to DDW+irradiation group. The PCE/NCE ratio continued to decline up to 36 h post-irradiation in both the groups. The dose response for MPCE and PCE/NCE ratio was linear quadratic, while it was linear for MNCE.

Animals↗