Penetration of VP-16 (etoposide) into human intracerebral and extracerebral tumors

Stewart, David J.; Richard, Marie-Claude; Hugenholtz, Herman; Dennery, Jean; Bélanger, Raymond; Gerin-Lajoie, Jean; Montpetit, V.; Nundy, Dev; Prior, Judith; Hopkins, Harry S.

doi:10.1007/bf00177899

Cited by 48 publications

(26 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…11 Etoposide has exhibited a good level of penetration into brain parenchyma as well, 12 and both of these agents have demonstrated good activity against recurrent brain tumors at conventional doses. [13][14][15] Finlay et al 20 treated 45 patients with high doses of etoposide (1500 mg/m 2 ) and thiotepa (900 mg/m 2 ) followed by autologous stem cell rescue; those investigators obtained a 23% CR ϩ PR rate in heavily pretreated patients and a 16% toxicity-related death rate.…”

Section: Discussionmentioning

confidence: 99%

“…Etoposide also has shown adequate penetration into the brain parenchyma. 12 Both thiotepa and etoposide have demonstrated good activity against recurrent brain tumors at conventional doses. [13][14][15] In the current report, we present the results obtained using an etoposide/thiotepa-based conditioning regimen in 27 patients who were affected with recurrent or newly diagnosed high-risk brain tumors.…”

mentioning

confidence: 99%

See 1 more Smart Citation

High‐dose thiotepa and etoposide in children with poor‐prognosis brain tumors

Biasin¹,

Mastrodicasa²,

Sandri³

et al. 2004

Cancer

View full text Add to dashboard Cite

BACKGROUNDOutcome data were analyzed for 27 patients who were affected with recurrent or newly diagnosed high‐risk brain tumors and who underwent high‐dose chemotherapy with triethylenethiophosphoramide (thiotepa) and etoposide in addition to autologous stem cell transplantation between May 1992 and September 2002.METHODSFifteen males and 12 females (median age, 11 years) were included in the study. Twelve patients had newly diagnosed high‐risk brain tumors, and 15 patients had recurrent brain tumors. The conditioning regimen consisted of thiotepa 900 mg/m2 and etoposide 1500 mg/m2 over 3 days starting on Day −5. Stem cell rescue was performed using bone marrow (BM) in 8 patients, peripheral blood stem cells (PBSCs) in 18 patients, and BM and PBSCs in 1 patient.RESULTSFor the BM group, neutrophil (PMN) engraftment was achieved on Day +14 (median value), whereas platelet (PLT) engraftment was achieved on Day +68 (median value). One patient did not achieve PLT engraftment. For the PBSC group, the PMN engraftment was achieved on Day +10.0 (median value), and the PLT engraftment was achieved on Day +15.5 (median value). Transplantation‐related toxicity (evaluated using the Bearman score) included Grade 2–3 mucositis in 16 patients, Grade 1 kidney toxicity in 6 patients, Grade 1 liver toxicity in 6 patients, and Grade 2 liver toxicity in 1 patient. Transplantation‐related mortality was observed in 1 patient (3.6%), who died of Candida pneumonia. The 3‐year overall survival (OS) rate was 44.6%, and the 3‐year event‐free survival (EFS) rate was 31%. There was a statistically significant difference in OS and EFS rates for patients who underwent ASCT and achieved complete remission compared with patients who had measurable disease.CONCLUSIONSThe results of the current study suggest that high‐dose chemotherapy followed by ASCT may be beneficial for patients who achieve complete remission before ASCT, whereas for other patients, new strategies are required. Cancer 2004. © 2004 American Cancer Society.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

High‐dose thiotepa and etoposide in children with poor‐prognosis brain tumors

Biasin¹,

Mastrodicasa²,

Sandri³

et al. 2004

Cancer

View full text Add to dashboard Cite

show abstract

“…29 Other agents, like VP-16 and thiotepa have also been used previously as monotherapies at high doses for the treatment of CNS lesions. 11,12,14,15 Previous reports by Finlay et al 8,20 using high-dose thiotepa and VP-16 with ABMR in CNS tumors indicated that this approach is feasible and active against recurrent tumors. The current paper summarizes the experience of an intensified protocol consisting of high-dose BCNU/thiotepa/VP-16 used in patients with newly diagnosed or recurrent disease.…”

Section: Discussionmentioning

confidence: 99%

“…A number of patients have been included in previous publications. Specifically, the patients referred to in Table 2 with the number 19, 29, 32, 33, 37, 20 3,7,8,12,13,15,30, 33, 21 19, 26 22 and 37. 23 Patient treatment was specified by protocols previously reviewed and approved by the Institutional Review Board of the treating institutions.…”

Section: Recurrent Disease Patientsmentioning

confidence: 99%

“…9 Carmustine (BCNU) and other nitrosoureas have been used to treat primary CNS malignancies. Thiotepa and etoposide (VP-16) have shown excellent and adequate CNS penetration [13][14][15] and have produced responses when given at conventional doses. 12,[16][17][18] The thiotepa/VP-16 combination appeared promising in the autologous bone marrow rescue (ABMR) setting for patients with recurrent CNS tumors.…”

mentioning

confidence: 99%

See 1 more Smart Citation

High-dose carmustine, thiotepa and etoposide followed by autologous bone marrow rescue for the treatment of high risk central nervous system tumors

Papadakis

Dunkel

Cramer

et al. 2000

Bone Marrow Transplant

View full text Add to dashboard Cite

Summary:Forty-two patients (29 newly diagnosed) with high grade gliomas (n = 37), medulloblastoma (n = 2) or nonbiopsied tumors (n = 3) with supratentorial (n = 24), brain stem (n = 11), posterior fossa (n = 5) or spinal (n = 2) location were eligible for this study with adequate organ function and no bone marrow tumor infiltration. Median patient age was 12.2 years (range, 0.7-46.8). A total of 600 mg/m 2 BCNU, 900 mg/m 2 thiotepa and 1500 or 750 mg/m 2 etoposide (VP-16) was administered followed by autologous bone marrow reinfusion (ABMR). Twenty-one newly diagnosed patients received local irradiation (RT) post ABMR. Nine early deaths were observed (21%), as well as one secondary graft failure. Half of the patients aged 18 years or older experienced toxic deaths, whereas only 15% of patients younger than 18 years experienced toxic death (P = 0.05). Of 25 evaluable newly diagnosed patients, 20% achieved complete remission (CR) and 4% partial remission (PR), while 28% remained in continuing complete remission (CCR) and 44% remained with stable disease prior to RT. Of eight evaluable patients with recurrent disease, one achieved CR and two PR, while one remained in CCR and four with stable disease for 1 to 110.2 months. Overall survival was 36%, 24% and 17% at 1, 2 and 3 years following ABMR, with three newly diagnosed patients and one patient treated for recurrent disease being alive, without disease progression 64.4, 67.0, 86.3 and 110.2 months after ABMR, respectively. The combination of high-dose BCNU/ thiotepa/VP-16 has substantial toxicity but definite activity for high risk CNS tumors. Similar protocols with lower toxicity merit further evaluation in both

show abstract

Front‐line chemotherapy with cisplatin and etoposide for patients with brain metastases from breast carcinoma, nonsmall cell lung carcinoma, or malignant melanoma

Franciosi¹,

Cocconi²,

Michiara³

et al. 1999

Cancer

234

View full text Add to dashboard Cite

BACKGROUND The conventional treatment of brain metastases not amenable to surgery is most often radiotherapy. Until now, pharmacologic issues related to the blood brain barrier (BBB) prevented a wide evaluation of chemotherapy. The authors previously reported that the combination of cisplatin (P) and etoposide (E) had strikingly high activity in patients with brain metastases from breast carcinoma. The purpose of this study was to assess, in a larger prospective study, the front‐line activity of that combination against brain metastases from breast carcinoma (BC), nonsmall cell lung carcinoma (NSCLC), and malignant melanoma (MM) in patients previously untreated with radiotherapy. METHODS From December 1986 to July 1993, 116 patients received P 100 mg/m2 on Day 1 and E 100 mg/m2 on Days 1, 3, and 5 or on Days 4, 6, and 8 every 3 weeks. An insignificant change in the E schedule using the same dose on a random basis assured the prospective enrollment and the registration of all cases. Six patients were not eligible and three patients were excluded from the analysis because they were lost to follow‐up shortly after the date of registration. One‐hundred seven patients were considered for analysis. The distribution according to the primary tumor site was BC in 56 patients (52%), NSCLC in 43 (40%), and MM in 8 (8%). The first evaluation of response was performed after two cycles. In cases of no disease progression, chemotherapy was continued to a maximum of six cycles. RESULTS Among the 56 patients with BC, 7 achieved complete response (CR) (13%), 14 achieved partial response (PR), 12 had no change (NC), 15 had progressive disease (PD), and 8 had insufficient treatment or response was not assessed. The CR plus rate was 38%. Among the 43 patients with NSCLC, 3 achieved CR (7%), 10 achieved PR, 15 had SD, 7 had PD, and 8 had insufficient treatment or response was not assessed. The CR plus PR rate was 30%. None of the eight patients with MM achieved an objective response. The median survival was 31 weeks for patients with BC (range, 0–287), 32 for patients with NSCLC (0–392+), and 17 for patients with MM (2–48). CONCLUSIONS The combination of P and E is effective for patients with brain metastases from BC and NSCLC. In this study, the response rate was of the same order as that reported for disseminated disease without central nervous system involvement. The survival figures compare favorably with some others reported in the literature for patients given radiotherapy. A randomized study is warranted to compare this chemotherapy followed by radiotherapy with radiotherapy alone for patients with brain metastases from BC or NSCLC not amenable to surgery or radiosurgery. Cancer 1999;85:1599–605. © 1999 American Cancer Society.

show abstract

Penetration of VP-16 (etoposide) into human intracerebral and extracerebral tumors

Cited by 48 publications

References 16 publications

High‐dose thiotepa and etoposide in children with poor‐prognosis brain tumors

High‐dose thiotepa and etoposide in children with poor‐prognosis brain tumors

High-dose carmustine, thiotepa and etoposide followed by autologous bone marrow rescue for the treatment of high risk central nervous system tumors

Front‐line chemotherapy with cisplatin and etoposide for patients with brain metastases from breast carcinoma, nonsmall cell lung carcinoma, or malignant melanoma

Contact Info

Product

Resources

About