scholarly journals Imatinib mesylate for targeting the platelet-derived growth factor β receptor in combination with fluorouracil and leucovorin in patients with refractory pancreatic, bile duct, colorectal, or gastric cancer—A dose-escalation Phase I trial

Cancer ◽  
2007 ◽  
Vol 109 (9) ◽  
pp. 1897-1904 ◽  
Author(s):  
Salah-Eddin Al-Batran ◽  
Akin Atmaca ◽  
Eberhard Schleyer ◽  
Claudia Pauligk ◽  
Christian Hosius ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Growth Factor ◽  
Bile Duct ◽  
Phase I ◽  
Imatinib Mesylate ◽  
Dose Escalation ◽  
Phase I Trial ◽  
Platelet Derived Growth Factor ◽  
Β Receptor

Platelet-Derived Growth Factor Receptor Inhibitor Imatinib Mesylate and Docetaxel: A Modular Phase I Trial in Androgen-Independent Prostate Cancer

2004 ◽  
Vol 22 (16) ◽  
pp. 3323-3329 ◽  
Author(s):  
Paul Mathew ◽  
Peter F. Thall ◽  
Donnah Jones ◽  
Cherie Perez ◽  
Corazon Bucana ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Phase I ◽  
Imatinib Mesylate ◽  
Phase I Trial ◽  
Growth Factor Receptor ◽  
Maximum Tolerated Dose ◽  
Platelet Derived Growth Factor ◽  
Bone Marrow Biopsies ◽  
Androgen Independent

Purpose To study the platelet-derived growth factor receptor (PDGFR) inhibitor imatinib mesylate in androgen-independent prostate cancer (AIPC), alone and in combination with docetaxel, we designed a modular phase I trial. Our goals were to (1) evaluate the toxicity and maximum-tolerated dose of docetaxel with imatinib, and (2) evaluate the decline of prostate-specific antigen (PSA) induced by imatinib alone, and imatinib and docetaxel. Patients and Methods Twenty-eight men with AIPC and bone metastases were enrolled to receive imatinib 600 mg daily lead-in for 30 days, then imatinib 600 mg daily and one of six possible doses of docetaxel weekly for 4 weeks every 6 weeks. Results During the imatinib lead-in module, one dose-limiting toxicity (DLT) event was observed, while two (7%) of 28 had PSA decline (both < 50%). With imatinib and docetaxel, cycle 1 DLT was found in three of 12 patients at docetaxel 30 mg/m2, in three of four patients at docetaxel 45 mg/m2, and in five of six patients at docetaxel 35 mg/m2. DLTs (n = 40 total events) were principally fatigue (35%) and nausea (20%). Eight (38%) of 21 had PSA decline greater than 50%, and six (29%) of 21 had PSA decline less than 50%. Serial PSA declines beyond 18 months were observed. PDGFR-expressing tumor declined on serial bone marrow biopsies with combination therapy alone. Conclusion With imatinib 600 mg daily, the maximum-tolerated dose of docetaxel was determined to be 30 mg/m2 weekly for 4 weeks every 6 weeks. Long-term responses were observed. The role of imatinib in modulating outcomes to docetaxel in AIPC is being tested in a randomized phase II trial.

Pediatric phase I trial and pharmacokinetic study of the platelet-derived growth factor (PDGF) receptor pathway inhibitor SU101

2004 ◽  
Vol 53 (6) ◽  
pp. 482-488 ◽  
Author(s):  
P. C. Adamson ◽  
S. M. Blaney ◽  
B. C. Widemann ◽  
B. Kitchen ◽  
R. F. Murphy ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phase I ◽  
Pharmacokinetic Study ◽  
Phase I Trial ◽  
Platelet Derived Growth Factor ◽  
Pdgf Receptor

Phase I trial of dose escalation with growth factor support in patients with previously untreated diffuse aggressive lymphomas: determination of the maximum-tolerated dose of ProMACE-CytaBOM.

1996 ◽  
Vol 14 (4) ◽  
pp. 1275-1281 ◽  
Author(s):  
L I Gordon ◽  
J Anderson ◽  
T M Habermann ◽  
J N Winter ◽  
J Glick ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phase I ◽  
Dose Escalation ◽  
Phase I Trial ◽  
Bone Marrow Involvement ◽  
Stage Iv ◽  
Dose Intensity ◽  
Maximum Tolerated Dose ◽  
Phase Ii Trials ◽  
Gm Csf

PURPOSE The aim of this study was to determine the maximum-tolerated dose (MTD) of cyclophosphamide, doxorubicin, etoposide, prednisone, bleomycin, cytarabine, methotrexate, and leucovorin (ProMACE-CytaBOM) when the myelotoxic drugs cyclophosphamide, doxorubicin, etoposide, and cytarabine are escalated. PATIENTS AND METHODS Thirty-eight eligible patients with diffuse aggressive non-Hodgkin's lymphoma were treated on a phase I trial of dose escalation using the ProMACE-CytaBOM regimen and granulocyte-macrophage colony-stimulating factor (GM-CSF; Schering, Kenilworth, NJ). Patients were treated with recombinant (r)GM-CSF 10 microg/kg/d subcutaneously from day 9 to 19. Twenty-seven patients had stage IV disease, four had stage III, and seven had bulky stage II. Half of the patients had bone marrow involvement. The median age was 45 years. RESULTS We found that the MTD was 200% for the escalated drugs in this regimen (although we never escalated above the MTD or defined by dose-limiting toxicity) and that the normalized dose-intensity (NDI; defined as the ratio of the received dose-intensity to the 100% dose-intensity of ProcMACE-CytaBOM) decreased with each cycle and was lower for the day-8 drug (cytarabine) than for the day-1 drugs. The complete response (CR) rate was 66%, and 92% of patients who achieved CR are alive without disease with a median follow-up time for survival of 3.6 years. CONCLUSION The MTD of cyclophosphamide, doxorubicin, etoposide, and cytarabine in the ProMACE-CytaBOM regimen given with growth factor support is 200%, and this dose should be tested in larger phase II trials.

Phase I trial of vendetanib and oral etoposide for recurrent malignant gliomas

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13016-e13016
Author(s):  
J. Herndon ◽  
J. Vredenburgh ◽  
D. Reardon ◽  
A. Desjardins ◽  
K. Peters ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phase I ◽  
Malignant Glioma ◽  
Dose Level ◽  
Dose Escalation ◽  
Phase I Trial ◽  
Malignant Gliomas ◽  
Oral Etoposide ◽  
Level 1 ◽  
Grade 3

e13016 Background: Recurrent malignant gliomas have a poor prognosis, with a median survival of 6–15 months, with grade 4 glioblastomas more aggressive than grade 3 anaplastic astrocytomas or oligodendrogliomas. Vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) are critically important in glioma biology. Vandetanib is a multi-kinase inhibitor, predominantly of VEGF and EGF. We report a phase I trial of vandetanib in combination with oral etoposide for recurrent malignant glioma. Methods: Patients with histologically documented recurrent grade 3 or grade 4 malignant glioma were eligible. Patients were treated with daily oral vandetanib and oral etoposide. The trial design was a modified 3 + 3 Phase I design, with the dose levels outlined below. Results: Eighteen patients have been accrued. There was more hematologic toxicity than expected, with 3/6 of the patients enrolled at dose level 1 developing grade 4 neutropenia. There were no DLT's at the -1 dose level. The protocol was amended to decrease the dose of etoposide to 50 mg daily for 21 days, then 7 days off and dose escalation of vandetanib started again at 100 mg daily. Six patients had no dose limiting toxicity at the new dose level 1 of vandetanib 100 mg daily and etoposide 50 mg daily. Dose escalation continues. There has been clinical activity, with patients remaining stable on study for multiple cycles. Conclusions: Vandetanib and oral etoposide appear to interact to produce more marrow toxicity than expected. A phase II trial is planned when the MTD of vandetanib with reduced dose etoposide is determined. [Table: see text] No significant financial relationships to disclose.

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