Phase I pilot study of oxaliplatin, infusional 5-FU, and cetuximab in recurrent or metastatic head and neck cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16027-e16027
Author(s):  
Jay S. Dalal ◽  
Joshua B. Greene ◽  
Craig C. Hofmeister ◽  
Ann Lau Clark ◽  
Joseph Clark
Keyword(s):  
Pilot Study ◽  
Phase I ◽  
Head And Neck ◽  
Dose Level ◽  
Maximum Tolerated Dose ◽  
Platinum Based Chemotherapy ◽  
Acneiform Rash ◽  
Level 1 ◽  
Level 2 ◽  
Experienced Grade

e16027 Background: Platinum-based chemotherapy including cisplatin, 5-fluorouracil (5-FU), and the EGFR-directed monoclonal antibody cetuximab, are active in the treatment of head and neck squamous cell carcinoma (HNSCC). Patients with inoperable recurrent or metastatic HNSCC have a poor prognosis and many have difficulty tolerating cisplatin-based regimens. Oxalipatin, a third-generation platinum derivative, has demonstrated antitumor activity and lacks many of the limiting side effects of cisplatin. We conducted a phase I pilot study to investigate the dose-limitation of oxaliplatin in addition to infusional 5-FU and cetuximab in patients with untreated recurrent or metastatic HNSCC. Methods: The planned dose escalation schedule included: dose level 1: oxaliplatin 100mg/m2 day 1, 5-FU CIV 750mg/m2 over 96 hours beginning day 1, and cetuximab 400mg/m2 cycle 1, day 1 (and 250mg/m2 weekly thereafter) on a 21-day cycle. Dose level 2: oxaliplatin 130mg/m2 day 1, 5-FU CIV 1000mg/m2 over 96 hours beginning day 1 and the same dose and schedule of cetuximab. Results: A total of 10 patients were accrued, consisting of 4 females and 6 males. The first seven were enrolled onto dose level 1 and the following three onto dose level 2. Dose level 1 was tolerated well with acceptable toxicity, including grade 1-2 oral mucositis, grade 1-2 fatigue, grade 1-2 acneiform rash, grade 1 nausea, grade 1-2 anemia and grade 1 transaminitis. All responses observed, (1 MR, 1 PR, 1 CR), were short-lived. Dose level 2 was more toxic than anticipated; 2 of 3 patients experienced grade 4 toxicities (mucositis, diarrhea, acute renal failure) requiring hospitalization with a treatment-related death in one of these patients. The phase I portion of the trial was therefore closed and dose level 1 is considered the maximum tolerated dose. Conclusions: The regimen of oxaliplatin 100mg/m2 day 1, infusional 5-FU 750mg/m2 over 96 hours beginning day 1, and cetuximab 400mg/m2 cycle 1, day 1 (with 250mg/m2 weekly thereafter), given on a 21-day cycle, has manageable toxicity; these doses are recommended for phase II evaluation in the treatment of unresectable or metastatic HNSCC.

Phase I trial of pemetrexed (P) in combination with cetuximab (C) and concurrent radiotherapy (RT) in patients (pts) with head and neck cancer (HNC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16516-16516
Author(s):  
R. Smith ◽  
M. V. Karamouzis ◽  
D. E. Heron ◽  
R. L. Ferris ◽  
S. Y. Lai ◽  
...  
Keyword(s):  
Phase I ◽  
Head And Neck ◽  
Dose Level ◽  
Growth Factor Receptor ◽  
Maximum Tolerated Dose ◽  
Neutropenic Fever ◽  
Igg1 Monoclonal Antibody ◽  
Starting Dose ◽  
Lower Dose Level ◽  
Level 1

16516 Background: P is a multitargeted antifolate that has demonstrated activity in HNC and radiosensitizing properties in animal models. C is a chimeric IgG1 monoclonal antibody directed against the epidermal growth factor receptor that has increased the survival of pts with stage III/IV HNC when added to RT. We conducted a phase I study to evaluate the dose-limiting toxicities (DLT) and maximum tolerated dose of P when combined with standard RT and C. Methods: Pts with high-risk HNC were enrolled and evaluated separately in 2 cohorts: pts with no prior head and neck RT (cohort A) and previously irradiated pts (cohort B). A loading dose of C 400 mg/m2 was given intravenously 7 days prior to starting RT followed by 250 mg/m2 weekly throughout RT. RT was given 2 Gy/day to a total dose of 70 Gy (cohort A) or 60–66 Gy (cohort B). P was administered intravenously on days 1 and 22 (and day 43 if >60 Gy was delivered) according to the following design: Starting dose level (0)-350 mg/m2, dose level (-1)-200 mg/m2, dose level (+1)-500 mg/m2. Additional pts could be treated at a lower dose level while other pts were being evaluated at a higher dose level. Results: 18 pts have been enrolled (A: 14; B:4). 2 pts in cohort A were not evaluable and replaced (1 pt was noncompliant due to transportation issues and 1 pt had sudden death attributable to aspiration). Histological types: squamous cell (13), undifferentiated (1), medullary thyroid (1), adenoid cystic (1), and adenosquamous carcinomas (2). In cohort A, 2 DLT (both neutropenic fever with ANC <500) occurred: 1/6 at dose level 0 and 1/6 at dose level -1. In cohort B, no DLT has occurred: 0/3 pts at dose level 0 and 0/1 pts at dose level +1. There were no grade (G) 4 non- hematologic toxicities. Other serious toxicities included: neutropenic fever (NF) with ANC <1000 (n=1), G 3/4 neutropenia (n=3/n=4), G 3 dysphagia (n=5), G 3 dermatitis (n=3), G 3 mucositis (n=4), G 3 fatigue (n=1), and G 3 anemia (n=1). Due to the development of 3 cases of NF in cohort A the protocol was amended and prophylactic antibiotics were added. Conclusions: The addition of P to RT and C was feasible in pts with or without a history prior RT. Neutropenia and in-field toxicities were predominant but manageable. Pts are currently being treated at dose level +1 (P 500 mg/m2). No significant financial relationships to disclose.

Phase I study of vandetinib in combination with gemcitabine and oxaliplatin in advanced solid malignancies.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3037-3037
Author(s):  
Peng Wang ◽  
Taofeek Kunle Owonikoko ◽  
Yan Lin ◽  
Ronald G. Stoller ◽  
Daniel P. Petro ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phase I ◽  
Dose Level ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Maximum Tolerated Dose ◽  
Cytotoxic Agents ◽  
Level 1 ◽  
Level 2

3037 Background: Vandentinib (VAN) is a tyrosine kinase inhibitor with activity against vascular endothelial growth factor receptor-2 (VEGFR-2) and 3 (VEGFR-3) as well as epidermal growth factor receptor (EGFR) and RET (‘rearranged during transfection’). Combinations of VEGFR kinase inhibitors and cytotoxic agents have been studied with interest, but have been associated with increased toxicity. This phase I trial evaluated the safety, tolerability and maximum tolerated dose of VAN in combination with gemcitabine (GEM) and oxaliplatin (OX). Methods: Subjects with advanced solid malignancy, ≤ 2 prior regimens with adequate hematologic, hepatic and renal function were eligible. GEM and OX were administered intravenously at 1000 mg/m2 and 85 mg/m2 respectively every 14 days. VAN was administered orally at two dose levels: level 1 (200 mg) and level 2 (300 mg) once daily continuously. After a maximum of 6 cycles of GEMOX, non-progressing patients were allowed to continue VAN until progression or intolerance. A dose level was determined to be tolerable if <2 DLTs out of 6 evaluable subjects were observed. Response was assessed by restaging scan after every 2 cycles. Results: A total of 20 subjects were enrolled in the study; 15 male, 5 female. Median age 62 years (47-68). Nine subjects were enrolled on dose level 1 and 11 subjects on dose level 2. One subject in dose level 1 experienced a deep venous thrombosis in cycle 1 deemed a DLT. Thrombocytopenia (worst-grade 3) as well as diarrhea and rash (worst-grade 2) were observed in several patients, without dose-limiting toxicity in cycle 1. Reversible posterior leukoencephalopathy was observed in 1 subject following abrupt self-discontinuation of an antihypertensive mediation. The recommended phase 2 dose was established as GEM (1000mg/m2) OX (85mg/m2) and VAN (300mg). One subject with refractory small cell lung cancer had a confirmed partial response, and 10 subjects (pancreas-7, bladder-2 and biliary-1) achieved stable disease ≥12 weeks. Conclusions: VAN in combination with GEM/OX was well tolerated at full doses of each of the 3 agents. Preliminary anti-tumor activity seen in refractory solid tumors supports further evaluation of this regimen.

scholarly journals Phase I study of the 177Lu-DOTA0-Tyr3-Octreotate (lutathera) in combination with nivolumab in patients with neuroendocrine tumors of the lung

2020 ◽  
Vol 8 (2) ◽  
pp. e000980
Author(s):  
Chul Kim ◽  
Stephen V Liu ◽  
Deepa S Subramaniam ◽  
Tisdrey Torres ◽  
Massimo Loda ◽  
...  
Keyword(s):  
Phase I ◽  
Dose Level ◽  
Neuroendocrine Tumors ◽  
Phase I Study ◽  
Somatostatin Receptors ◽  
Atypical Carcinoid ◽  
Platinum Based Chemotherapy ◽  
Level 1 ◽  
Grade 3 ◽  
Level 2

BackgroundLutathera is a 177Lutetium-labeled somatostatin analog approved for the treatment of gastroenteropancreatic neuroendocrine tumors (NETs). Somatostatin receptors are expressed in small cell lung cancer (SCLC). Nivolumab, an anti-PD-1 antibody, may act synergistically with lutathera to generate antitumor immunity. We conducted a phase I study of lutathera plus nivolumab in patients with advanced NETs of the lung.MethodsPatients with relapsed/refractory extensive-stage SCLC (ES-SCLC), non-progressing ES-SCLC after first-line platinum-based chemotherapy, or advanced grade I-II pulmonary NETs were eligible. The primary objective was to determine the recommended phase 2 dose (RP2D). The phase I portion followed a standard 3+3 design, assessing two dose levels (dose level 1: lutathera 3.7 GBq every 8 weeks for four doses with nivolumab 240 mg every 2 weeks; dose level 2: lutathera 7.4 GBq every 8 weeks for four doses with nivolumab 240 mg every 2 weeks).ResultsNine patients were enrolled (six ES-SCLC, two pulmonary atypical carcinoid, one high-grade pulmonary neuroendocrine carcinoma). No dose-limiting toxicities (DLTs) were observed at dose level 1. At dose level 2, one patient with refractory ES-SCLC developed a DLT (grade 3 rash). The most common treatment-related adverse events (TRAEs) were lymphopenia (n=7), thrombocytopenia (n=4), anemia (n=3), and nausea (n=3). The most common grade 3 TRAE was lymphopenia (n=4). Among the seven patients with measurable disease, one patient with ES-SCLC had a partial response. Two patients with pulmonary atypical carcinoid had stable disease lasting 6 months. The RP2D was dose level 2.ConclusionsLutathera plus nivolumab was well tolerated and showed signs of antitumor activity. This combination warrants further exploration.Trial registration numberNCT03325816

scholarly journals ACTR-63. PHASE I DOSE ESCALATION STUDY OF PROCASPASE ACTIVATING COMPOUND-1 (PAC-1) IN COMBINATION WITH TEMOZOLOMIDE IN PATIENTS WITH RECURRENT ANAPLASTIC ASTROCYTOMA OR GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi28-vi28
Author(s):  
Matthias Holdhoff ◽  
Martin Nicholas ◽  
Richard Peterson ◽  
Oana Danciu ◽  
Stefania Maraka ◽  
...  
Keyword(s):  
Dose Level ◽  
Dose Escalation ◽  
Anaplastic Astrocytoma ◽  
Caspase 3 ◽  
Phase 1 ◽  
Maximum Tolerated Dose ◽  
Pharmacokinetic Data ◽  
Dose Escalation Study ◽  
Level 1 ◽  
Level 2

Abstract BACKGROUND Procaspase activating compound -1 (PAC-1) is a small molecule that catalyzes conversion of procaspase-3 to caspase-3 which induces apoptosis in cancer cells. Glioblastoma (GBM) is among the tumors with high concentrations of procaspase-3 and low levels of caspase-3. PAC-1 crosses the blood brain barrier and has been shown to synergize with temozolomide (TMZ) in canine malignant glioma and meningioma that arise spontaneously. METHODS This is a multicenter phase 1 dose-escalation study to assess the maximum tolerated dose (MTD) of PAC-1 administered days 1–21 in combination with TMZ days 8–12 at a dose of 150 mg/m2 of each 28 day cycle in subjects with recurrent anaplastic astrocytoma (AA) or GBM. A modified Fibonacci 3 + 3 design is used with up to 4 dose levels of PAC-1 (375, 500, 625 and 750 mg/day). Neurologic toxicity, including cognitive function, is closely monitored throughout the trial. INTERIM DATA: A total of 14 subjects have been enrolled to-date. Of these, 7 at dose level 1, PAC-1 375 mg/day (6 GBM, 1 AA; median age 58y, range 25–75) and 7 at dose level 2, PAC-1 500 mg/day (5 GBM, 2 AA; median age 51y, range 35–60). Best responses to-date were 2 subjects with a partial response and 2 with stable disease. Grade 3 (hepatotoxicity) and 4 (cerebral edema) was reported as possibly related to PAC-1 in 1 patient at dose level 1. The median number of cycles received was 4 (range, 1–12+) at dose level 1 and 2 (range, 1–3) at dose level 2. Enrollment to dose level 2 has been completed and data analysis is ongoing. Updated response and toxicity as well as pharmacokinetic data will be presented.

Oxaliplatin, Fludarabine, Cytarabine, and Rituximab Combination Therapy Induces High Response Rates in Agressive Chronic Lymphocytic Leukemia (CLL) and Richter's Syndrome (RS).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3443-3443 ◽  
Author(s):  
Apostolia-Maria Tsimberidou ◽  
William Wierda ◽  
William Plunkett ◽  
Susan O'Brien ◽  
Thomas J. Kipps ◽  
...  
Keyword(s):  
Phase I ◽  
Dose Level ◽  
Phase Ii ◽  
Research Funding ◽  
Response Rates ◽  
Off Label ◽  
Level 3 ◽  
Level 1 ◽  
Grade 3 ◽  
Level 2

Abstract Abstract 3443 Poster Board III-331 Introduction The first Phase I-II clinical trial of oxaliplatin, fluradabine, cytarabine (Ara-C), and rituximab (OFAR1) demonstrated significant activity in refractory CLL and RS (Tsimberidou et al, J Clin Oncol, 2008;26:196). To enhance the response rate and decrease myelosuppression, the dose of oxaliplatin was increased to 30mg daily, the dose of Ara-C was decreased to 0.5g/m2 daily and the optimal number of days of fluradabine and Ara-C administration was explored (OFAR2). Methods In a Phase I-II study of OFAR2, patients were treated with oxaliplatin 30mg/m2, D1-4; fludarabine 30mg/m2, Ara-C 0.5g/m2; rituximab 375mg/m2, D3; and pelfigrastim 6mg, D6. Fludarabine and Ara-C were given on D2-3 (dose level 1) D2-4 (dose level 2) or D2-5 (dose level 3); courses were repeated every 4 weeks. Patients received prophylaxis for tumor lysis, DNA viruses, and PCP. A “3+3” design was used and the planned number of patients in the Phase II was 90 (CLL, 60; RS, 30). Results Ninety-one patients (CLL, 67; RS, 24) have been treated to date: Phase I, 12 patients (by dose level: 1, n=3; 2, n=6; and 3, n=3). DLTs were noted in 2 of 3 patients on dose level 3 (G4 diarrhea, 1; G4 neutropenic sepsis, 1); thus, dose level 2 was the MTD. Seventy-nine patients (relapsed CLL, 58; RS, 19) have been treated in the Phase II portion of the study. Patient characteristics were as follows: age > 60 years, 65%; 17p deletion, 38%; 11q deletion, 13%; 13q deletion, 16%; trisomy 12, 21%; no findings, 12%; unmutated IgVH, 80%; ZAP70-positive, 75%; and CD38 ≥30%, 58%. Response in patients treated in the Phase II recommended dose is shown in Table (evaluable, 67). The overall response rates in patients with 17p and 11q deletions were 48% and 55%, respectively. The median survival duration was 21 months (CLL, 21 months; RS, 9.5 months). At 18 months, the survival rates in patients with 17p and 11q deletions were 66% and 76%, respectively. Twelve patients underwent stem cell transplantation after OFAR2 (as post-remission therapy, n=10; as salvage, n=2). Overall, 196 cycles were administered. Grade 3-4 neutropenia, thrombocytopenia, and anemia were noted in 63%, 72%, and 39% of patients and in 57%, 70%, and 25% of cycles and Grade 3-4 infections in 19% of patients. Conclusion Preliminary results demonstrated that OFAR2 induced response in 40% of patients with RS and 63% of patients with relapsed/refractory CLL. OFAR2 had antileukemic activity in patients with 17p deletion. Clinical outcomes appeared to be superior to those of OFAR1 in refractory CLL, whereas results of OFAR1 appeared to be superior to those of OFAR2 in RS. Accrual is ongoing. Disclosures Tsimberidou: ASCO: ASCO Career Development Award; Sanofi: Research Funding. Off Label Use: Oxaliplatin is used off-label. Wierda:Genentech: Honoraria; Bayer, Sanofi-Aventis, Abbott, GSK: Research Funding; GSK, Trubion, Ligand, Genentech, Medimmune, Abbot: Consultancy; Celgene: Speakers Bureau. Plunkett:Sanofi-Aventis: Research Funding. O'Brien:Genentech: Research Funding; Sanofi: Consultancy. Kipps:NCI: Grant P01CA-81534.

Final Report of a Phase I Study of Clofarabine Plus High Dose Melphalan as a Conditioning Regimen for Allogeneic Transplantation

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 528-528
Author(s):  
Mark Kirschbaum ◽  
Anthony Selwyn Stein ◽  
Paul Frankel ◽  
Leslie Popplewell ◽  
Robert w Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Phase I ◽  
Dose Level ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Level 3 ◽  
Level 1 ◽  
Level 2 ◽  
Reduced Intensity

Abstract Abstract 528 Background: Allogeneic Stem Cell transplantation remains the only curative treatment modality for hematologic malignancies such as AML, ALL, and MDS. Reduced intensity regimens were designed which replaced the alkylating agent cyclophosphamide with the purine nucleoside antimetabolite, fludarabine, a potent immunosuppressive with a substantially milder toxicity profile. Clofarabine is a purine nucleoside analogue designed to exploit a double halogen strategy which confers resistance to adenosine deaminase, increases stability and bioavailability and makes the drug more efficient than fludarabine at inhibiting ribonucleotide reductase (RNR) and disrupting mitochondrial function, leading to apoptosis. Clofarabine is potentially a superior antileukemic agent as compared with fludarabine, thus enhancing the activity of the conditioning regimen. Aims: To evaluate a novel clofarabine containing regimen as conditioning for adult fully matched allogeneic stem cell transplant. Methods: phase I dose escalation: clofarabine (dose level 1 = 30 mg/m2, dose level 2 and 3 =40 mg/m2) IV daily days –7 to day –3 infused over 30 minutes IV, plus Melphalan (dose level 1 and 2, 100mg/m2, dose level 3, 140 mg/m2) administered over 30 minutes IV on day –2. Related or unrelated allogeneic stem cells were infused on day 0. GVHD prophylaxis: initially cyclosporine plus mycophenolate, then tacrolimus plus sirolimus was adopted as per City of Hope standard of care. Patients (pts) age ≥ 18 years with AML, ALL, MDS in either CR1, CR2 or in relapse (up to 50% marrow blasts), not deemed eligible for standard transplant regimens by the attending physician, or at high risk for relapse, are eligible. Results: 16 eligible pts, all with AML, have been treated thus far, 7,males, 9 females, with a median age of 63 years (30 – 66). Seven pts were in CR1, 2 pts were in CR2, 4 pts where induction failures, and 3 pts were in first relapse. Grade 3 non-hematologic toxicities included elevation of transaminases, diarrhea, and hyponatremia. No dose limiting toxicities (DLT) were seen in the 3 pts treated at dose level 1. One patient in dose level 2 died prior to engraftment due to hepatic, renal, and infectious toxicities; that dose level has been expanded to 12 patients and no further DLTs were seen. The first patient treated at dose level 3 developed multiorgan failure and died prior to engraftment. Given the excellent results seen in the two previous cohorts we opted not to dose escalate any further patients beyond clofarabine 40 mg/m2 and melphalan 100 mg/m2. Three patients with primary induction failure received an unrelated donor graft and had complete engraftment and obtained remission. The median time to ANC recovery is 14 days and to platelet recovery is 16 days (see table). Mild acute skin graft versus host disease (GvHD) was seen in five patients, mild chronic GvHD in four patients, one patient developed severe chronic GVHD of the liver and died at day 201 from CNS bleed due to tacrolimus-sirolimus related TTP-HUS. Of the 14 patients that successfully completed transplant (no DLT or engraftment difficulty), only one patient has relapsed, with median follow-up of 10.5 months (range 4–24). Conclusion: The combination of clofarabine and melphalan is a well tolerated reduced intensity conditioning regimen with enhanced anti-leukemia activity leading to complete engraftment of related and unrelated fully matched allogeneic stem cells. Complete engraftment with prolonged disease free survival was seen at both dose levels 1 and 2. Disclosures: Off Label Use: clofarabine as a component of the conditioning regimen for allogeneic transplant.

A Phase I Study of Idarubicin Dose Escalation for Remission Induction Therapy in Acute Myeloid Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1344-1344
Author(s):  
Mark Lee ◽  
Sung-Yong Kim
Keyword(s):  
Acute Myeloid Leukemia ◽  
Platelet Count ◽  
Phase I ◽  
Dose Level ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Phase I Study ◽  
Level 1 ◽  
Level 2 ◽  
Acute Myeloid

Abstract The maximum tolerated dose (MTD) of idarubicin has been acknowledged to be 12-15 mg/m2/day for 3 days for acute leukemias. Its MTD should be reevaluated in the treatment of acute myeloid leukemia (AML) in the era of granulocyte colony-stimulating factor and better supportive care. We conducted a phase I study to investigate the safety of escalating doses of idarubicin in combination with cytarabine 100 mg/m2/day for 7 days for previously untreated AML. The starting dose of idarubicin was 12 mg/m2/day for 3 days with dose escalations by 3 mg/m2/day. Cohorts of three patients were treated at each dose level, and the idarubicin dose was escalated up to 18 mg/m2/day until at least two patients among a cohort of three to six patients experienced the dose-limiting toxicities (DLTs) (traditional 3+3 design for phase I clinical trials: J Natl Cancer Inst 2009;101:708). Hematologic DLTs were defined as the time to recovery of neutrophils {absolute neutrophil count (ANC) ≥500/μL} or platelets (platelet count ≥20,000/μL) exceeded 42 days after the start of induction therapy (J Clin Oncol 2004;22:4290). Non-hematologic DLTs were defined as grade 4 or 5 toxicities (Leukemia 1998;12:865). We adopted the NCI CTCAE v3.0 to grade the hematologic and non-hematologic toxicities. Thirteen adult patients were enrolled in the study, but two and two were excluded at level 1 and level 2, respectively, because they received reinduction therapy for resistant disease within 4 weeks after the start of the assigned induction therapy. Consequently, nine patients were evaluable for the phase I study. The median times to recovery of neutrophils (ANC ≥500/μL) after the start of induction therapy at level 1, level 2, and level 3 were day 20 (range, 19-22), day 19 (range, 17-20), and day 25 (range, 21-26), respectively. The median times to recovery of platelet (platelet count ≥20,000/μL) at each level were day 20 (range, 19-23), day 20 (range, 16-34), and day 24 (range, 20-35), respectively. Therefore, grade 4 hematologic toxicities were observed at all 3 levels; however, these hematologic toxicities did not meet the criteria of the hematologic DLTs as defined in this study. There was any instance of grade 4 non-hematologic toxicity at each dose level. No death associated with the induction treatment was observed in this trial. Hematologic and non-hematologic DLTs as defined above were not observed at all 3 dose levels; therefore, idarubicin 18 mg/m2/day for 3 days could be defined as the MTD for this trial. Disclosures No relevant conflicts of interest to declare.

Docetaxel and capecitabine for previously treated metastatic colorectal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13579-13579
Author(s):  
T. E. O’Brien ◽  
E. Newton ◽  
J. Trey ◽  
E. Crum
Keyword(s):  
Colorectal Cancer ◽  
Phase I ◽  
Dose Level ◽  
Low Dose ◽  
Metastatic Breast ◽  
Human Colon Cancer ◽  
Level 3 ◽  
Previously Treated ◽  
Level 1 ◽  
Level 2

13579 Background: Docetaxel (D) induces human colon cancer cell lines to upregulate thymidine phosphorylase, an enzyme which activates capecitabine (C) to its cytotoxic form. This provided rationale for adding low dose D to C in patients with colorectal cancer (CRC). Although this combination has been established in metastatic breast cancer, it has not been evaluated in CRC. Because of concerns of toxicity in a pretreated population, we performed a phase I trial in patients with previously treated CRC. Methods: Eligibility: At least 1 prior treatment for metastatic disease; ECOG PS 0–1; adequate organ function. Design: Phase I, dose escalation. D, IV, days 1 & 8, and C, PO BID days 5–18, repeated q21days. Dose Level 1: D=15mg/m2, C=1000mg/m2; Level 2: D= 15 mg/m2, C= 1100 mg/m2; Level 3: D= 20 mg/m2, C= 1100 mg/m2; Level 4: D=20mg/m2, C=1250mg/m2. Results: 13 patients have thus far been treated. 11 are evaluable for toxicity and 10 for response (1 at dose level 4 was taken off study due to non-compliance before completion of cycle 1; another died of progressive cancer before completing cycle 1 at dose level 4; another is evaluable for toxicity but not yet for response). 9 with colon, 4 with rectal primary sites. Median follow-up= 5 mo (1–19 mo). Med age= 59 (30–75); #prior regimens for met disease 1–2, all of which were 5-FU based. Toxicities No dose limiting toxicities (DLT) until Dose Level 4. Dose Level 1: 1/3 developed grade 2 diarrhea and hand-foot syndrome and delayed grade 3 hand-foot; Dose Level 2: 2/3 developed grade 2 toxicities (hand-foot in one and diarrhea in the other); Dose Level 3: 1/3 developed delayed grade 2 hand-foot; Dose Level 4: 1 patient with delayed grade 2 hand-foot and grade 1 eye tearing; another developed DLT (grade 4 stomatitis/dehydration). Response 6/10 patients progressed after 2 cycles; 2 pts had stable disease, one lasting 4.6 mo; 2 patients had a partial response, one of which lasted 9 mo. The latter case had refractory disease to FOLFOX 4 but a 78% reduction in her liver metastases to D+C. Conclusions: The combination of low dose docetaxel, used as chemosensitizing agent, with capecitabine in this pretreated group of patients with metastatic CRC appears to be well tolerated, with no DLTs seen until Dose Level 4, and has modest activity. MTD determination awaits further accrual. No significant financial relationships to disclose.

Gefitinib (ZD-1839) with concurrent docetaxel and conformal three-dimensional thoracic radiation followed by consolidative docetaxel/gefitinib for patients with stage III NSCLC: A phase I study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18165-18165
Author(s):  
A. Blackstock ◽  
J. Petty ◽  
T. Oaks ◽  
M. Porosnicu ◽  
H. Clark ◽  
...  
Keyword(s):  
Phase I ◽  
Dose Level ◽  
Three Dimensional ◽  
Maximum Tolerated Dose ◽  
Stage Iii ◽  
3 Dimensional ◽  
Thoracic Radiation ◽  
Stage Iii Nsclc ◽  
Experienced Grade ◽  
Grade Iii

18165 Background: The safety of 3-dimensional (3D) conformal thoracic radiation delivered with concurrent gefitinib/docetaxel chemotherapy in patients with inoperable stage III NSCLC has not been evaluated. Methods: Patients with inoperable stage III NSCLC received weekly intravenous (i.v.) docetaxel starting at a dose of 15 mg/m2 escalating to 30 mg/m2 in 5 mg/m2 increments and daily gefitinib (250 mg given orally). Patients recieved concurrent thoracic radiation to a dose of 70 Gy utilizing 3-D techniques. The chemoradiation therapy was followed by 2 cycles of consolidative docetaxel (75 mg/m2) given q 21 days and gefitinib 250 mg p.o. for 1 year or until disease progression. Results: Beginning December 2003, 15 patients have been entered to date to this IRB approved phase I trial to determine the maximum tolerated dose of weekly docetaxel when given concurrent with gefitinib and thoracic radiation. The dose-limiting toxicities (DLT) observed were primarily non-hematologic and occured at dose level 3 (25 mg/m2). One patient experienced grade III esophagitis that resulted in a grade III dehydration, a second patient experienced grade III diarrhea while a third patient suffered a grade V interstitial pneumonitis, believed to be related to the gefinitib. While 14 of 15 patients completed the chemoradiation portion of the study and 2 patients completed all planned therapy, 4 patients progressed during therapy, 3 patients discontinued treatment due to toxicity, and 2 patients refused to continue treatment. The median and 1-year survival thus far is 21 months and 56%, respectively. Conclusions: 70 Gy conformal thoracic radiation and concurrent gefitinib/docetaxel thus far appears feasible but with modest toxicity. The study is currently enrolling patients at the weekly 20 mg/m2 docetaxel dose level concurrent with 250 mg of daily gefitinib. This study was supported in-part by Sanofi-Aventis and Astra Zeneca. No significant financial relationships to disclose.

A dose-escalating phase I study of biweekly docetaxel in older men with hormone refractory prostate cancer (HRPC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16117-e16117
Author(s):  
J. McDevitt ◽  
R. Hauser ◽  
J. Simon ◽  
L. Balducci
Keyword(s):  
Phase I ◽  
Dose Level ◽  
Phase I Study ◽  
Assessment Tool ◽  
Maximum Tolerated Dose ◽  
Self Report ◽  
Weekly Dose ◽  
Level 3 ◽  
Level 1 ◽  
Dose Levels

e16117 Background: Docetaxel has been shown to be effective and is used in the treatment of HRPC. This phase I study is designed to investigate the maximum tolerated dose, tolerability and activity of docetaxel administered on a biweekly schedule in older patients with HRPC. This study will also explore the feasibility of a self-report geriatric assessment tool in this population. Methods: HRPC patients with progression of metastatic disease during hormonal therapy received docetaxel q 2 wks at dose levels of 40 (level 0), 45 (level 1), 50 (level 2), or 55 mg/m2 (level 3). The trial is a conventional phase I 3+3 dose-escalation design. Treatment was continued until progression, refused further treatment, or unacceptable toxicity. Patients were given the Vulnerable Elders Survey (VES-13) for completion every 4 weeks. Results: 16 patients were enrolled in the study. All are evaluable for toxicity, 10 for response. Pts had a median (range) age 76 (72–87). Median doses administered was 6 (range 3–19). The maximum tolerated dose (MTD) was not reached in the study. No dose limiting side effects were reported for any of the dosing levels in the 8 week assessment period. Five patients had a ≥50% decline in serum PSA on two consecutive measurements taken at least 2 weeks apart. Of the 10 patients with measureable disease, 2 patients (one at dose level 0 and one at dose level 3) achieved a complete response, 2 patients (one at dose level 1 and one at dose 2) achieved a partial response, and 3 patients had stable disease (one each at dose levels 1, 2, and 3). At the time of entry onto the study, 4 patients required narcotic analgesics for bone pain; after treatment, 1 (25%) discontinued their pain medications. The completion rate of the Vulnerable Elders Survey (VES-13) was 94.6%. Conclusions: Biweekly docetaxel can be safely administered in older metastatic HRPC patients and showed activity. For phase II evaluation, a bi-weekly dose of 55 mg/m2 appears to be suitable. The administration of the VES-13 was feasible in this population. [Table: see text]

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