Phase II Study of Capecitabine in Patients With Fluorouracil-Resistant Metastatic Colorectal Carcinoma

2004 ◽  
Vol 22 (11) ◽  
pp. 2078-2083 ◽  
Author(s):  
Paulo M. Hoff ◽  
Richard Pazdur ◽  
Yvonne Lassere ◽  
Susan Carter ◽  
Dvorit Samid ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Sequential Analysis ◽  
Single Agent ◽  
Clinical Activity ◽  
Metastatic Colorectal Carcinoma ◽  
Eligibility Criteria ◽  
Group Sequential ◽  
First Line Therapy ◽  
Kaplan Meier ◽  
Hand Foot Syndrome

Purpose Capecitabine is an oral fluoropyrimidine converted to fluourouracil (FU) preferentially in tumor tissue. It has proven clinical activity against colorectal cancer when used as first-line therapy. The objectives of this study were to assess the safety and efficacy of capecitabine in patients with metastatic colorectal carcinoma who progressed despite previous FU therapy. Patients and Methods According to the group sequential analysis design of this study, accrual would stop if no responses were observed in the first 20 patients treated. If one or more objective responses were confirmed, the trial would be expanded. Patients received capecitabine 1,250 mg/m2 twice a day for 14 days, every 3 weeks. Tumor lesions were assessed every 6 weeks, and patients were followed for survival every 3 months after completing treatment. Results Twenty-three patients were enrolled onto the study; 22 fulfilled all the eligibility criteria. No objective responses were observed among the 22 eligible patients; 11 patients (50%) had stable disease for a median duration of 141 days (range, 88–289 days). The Kaplan-Meier estimate of median time to disease progression was 64 days (95% CI, 41 to 134 days). The median survival time estimate was 389 days (95% CI, 267 to 637 days). The most frequent treatment-related adverse events were hand-foot syndrome, diarrhea, and nausea or vomiting. There were no grade 4 toxicities and no treatment-related deaths. Conclusion Single-agent capecitabine in patients with metastatic colorectal carcinoma refractory to FU showed no objective responses and clinical benefit that was, at best, modest. The use of capecitabine in combination with other treatments in this patient population is under investigation.

scholarly journals Cost-effectiveness projections of oxaliplatin and infusional fluorouracil versus irinotecan and bolus fluorouracil in first-line therapy for metastatic colorectal carcinoma

Cancer ◽  
2005 ◽  
Vol 104 (9) ◽  
pp. 1871-1884 ◽  
Author(s):  
Bruce E. Hillner ◽  
Deborah Schrag ◽  
Daniel J. Sargent ◽  
Charles S. Fuchs ◽  
Richard M. Goldberg
Keyword(s):  
Cost Effectiveness ◽  
Colorectal Carcinoma ◽  
Metastatic Colorectal Carcinoma ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Cetuximab in the first-line therapy of metastatic colorectal carcinoma: not so CRYSTAL clear

2008 ◽  
Vol 4 (6) ◽  
pp. 741-744 ◽  
Author(s):  
Alastair CJ Windsor ◽  
Richard Cohen ◽  
Long R Jiao ◽  
Justin Stebbing
Keyword(s):  
Colorectal Carcinoma ◽  
Metastatic Colorectal Carcinoma ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Phase II study of irofulven in recurrent or metastatic gastric cancer: A Cancer Therapeutic Research Group (CTRG) study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14105-14105
Author(s):  
H. C. Chung ◽  
W. Yeo ◽  
S. Y. Rha ◽  
M. Boyer ◽  
S. Y. Ong ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Study Drug ◽  
Metastatic Gastric Cancer ◽  
Eligibility Criteria ◽  
First Line Therapy ◽  
Kaplan Meier ◽  
Impact On Survival ◽  
Grade 3 ◽  
Therapeutic Research

14105 Background: Cytotoxic chemotherapy has been widely used in patients (pts) with advanced or metastatic gastric cancer, but the reported high response rates in phase II settings have not been confirmed by randomized trials. Moreover, the therapeutic impact on survival has been modest. The purpose of this study was to evaluate Irofulven, a DNA interacting acylfulvene analog, as first line therapy for pts with recurrent or metastatic gastric cancer. Methods: The main eligibility criteria were: Histologically or cytologically confirmed disease; age > 18 yrs; ECOG ≤ 2; measurable disease; no prior chemotherapy for recurrent or metastatic disease; life expectancy > 3 months. Irofulven was given at 0.45 mg/kg i.v. over 30-min infusion (max. 50 mg), on Day 1 and 8, every 3 weeks. The primary endpoint was treatment response and toxicity; the secondary end-point was survival. A 2-stage phase II design was used. In the first stage, the target enrollment was 20, if ≤ 2 responses were observed, the study would be stopped and the treatment concluded to be ineffective; if ≥ 6 responses were observed, the study drug would be concluded to be active. Otherwise, another 15 pts would be entered into the second stage. Survival was constructed using the Kaplan-Meier method. All patients entering the trial were included in the survival analysis. Results: 23 pts were entered into the first stage. The median no. of cycles per pt was 2 (range: 1–6). 2 pts (9%) had ≥ 1 week delay in administration of subsequent cycle of chemotherapy. For the day 8 chemotherapy, 7 pts (30%) required dose reductions; 5 (22%) had dose omitted. 22% and 17% pts developed grade 3/4 anemia and neutropenia respectively. There was no grade 4 thrombocytopenia or neutropenic fever. Of the 20 evaluable pts, no responses was observed, 3 pts had stable disease after 2 cycles of treatment which was not confirmed by a further assessment. Median overall survival was 6.05 months (95% CI 4.55–9.39). Conclusions: Irofulven was tolerated at the described dose but showed no evidence of antitumor activity in patients with advanced gastric cancer. Acknowledgement: The study was sponsored by the Division of Cancer Treatment and Diagnosis, National Cancer Institute, U.S.A, and its collaborator MGI Pharma, Inc. No significant financial relationships to disclose.

Continuous daily administration of sunitinib in patients (pts) with cytokine-refractory metastatic renal cell carcinoma (mRCC): Updated results

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5040-5040 ◽  
Author(s):  
S. Srinivas ◽  
J. Roigas ◽  
S. Gillessen ◽  
U. Harmenberg ◽  
P. H. De Mulder ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Kinase Inhibitor ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Eligibility Criteria ◽  
Best Response ◽  
Hand Foot Syndrome

5040 Background: Sunitinib malate, an oral, multitargeted tyrosine kinase inhibitor of multiple receptors, showed significant efficacy in 168 pts with cytokine refractory mRCC, with a 42% objective response rate (ORR) and progression-free survival (PFS) of 8.2 months at 50 mg/day (4 weeks on treatment, 2 weeks off) per investigator assessment (Motzer et al. JAMA 2006;295:2516–24). This study was designed to determine the efficacy and safety of single-agent sunitinib when administered in a continuous 37.5 mg/day regimen. Methods: Pts with histologically proven mRCC, refractory to a cytokine-based regimen, were enrolled in this open-label, multicenter, phase II study. Eligibility criteria included measurable disease, ECOG PS 0/1, and adequate organ function. Pts were randomized to receive sunitinib in the morning (AM) or in the evening (PM) at a dose of 37.5 mg/day, with individual doses subsequently titrated based on tolerability. The primary endpoint was RECIST-defined ORR. Secondary endpoints included PFS, adverse events (AEs) and quality of life measures. Results: 107 pts were randomized to AM (54) or PM (53) dosing and have been on study a median of 6.8 months (0.4 to 13.3). As of October 2006, 55 pts have discontinued due to progression (37 pts [35%]), AEs (17 pts [16%]), and 1 consent withdrawal (1%); 47 pts (44%) were dose reduced to 25 mg/day due to grade 2/3 AEs, the most frequent being: asthenia (12%), hand-foot syndrome (8%), and diarrhea (5%). The most commonly reported (=5% of pts) grade 3/4 AEs were hypertension (10%), asthenia (9%), hand-foot syndrome (9%), anorexia (8%), and diarrhea (6%). 31 pts (29%) were maintained on continuous sunitinib at 37.5 mg/day, and 29 (27%) were escalated to 50 mg/day. There were no significant differences between pts who received AM or PM dosing. Quality of life results will be presented. The best response by RECIST per investigator assessment shows an ORR of 19% with 43 pts (40%) with =6 months of stable disease. The median PFS is 8.3 months. Conclusions: Sunitinib 37.5 mg/day continuous dosing has a manageable safety profile and demonstrates promising clinical benefit as second-line therapy in mRCC. This regimen provides alternative sunitinib dosing that can be explored in combination studies. No significant financial relationships to disclose.

Phase I study of anti-PlGF monoclonal antibody (mAb) RO5323441 (RO) and anti-VEGF mab bevacizumab (BV) in patients with recurrent glioblastoma (GBM).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2092-2092 ◽  
Author(s):  
Ulrik Niels Lassen ◽  
Oliver L. Chinot ◽  
Catherine McBain ◽  
Morten Sorensen ◽  
Vibeke Andree Larsen ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Single Agent ◽  
Tumor Stage ◽  
Recurrent Glioblastoma ◽  
Clinical Activity ◽  
Organ Function ◽  
Vegf Inhibitors ◽  
Eligibility Criteria ◽  
Prior Therapy ◽  
Clinical Trial Information

2092 Background: BV inhibits VEGF and is approved for progressive GBM following prior therapy. The placental growth factor (PlGF) is a member of the VEGF family and PlGF expression has been shown to correlate with tumor stage and survival in several human malignancies. In cancer patients (pts) PlGF is up-regulated upon treatment with VEGF inhibitors. RO is a humanized IgG1 mAb directed against PlGF that has demonstrated antitumor activity in an orthotopic GBM model. Single agent RO was previously tested in advanced solid tumors. Methods: Eligibility criteria included histologically confirmed GBM with documented radiographic progression upon front line therapy, ≥18 years of age, KPS ≥70, adequate bone marrow reserve and organ function. Prior treatment with VEGF/PLGF targeted therapies was not permitted. Three to six pts were enrolled per dose level (DL), the MTD defined as the dose with DLTs ≤ 1/6 pts during 28-days of cycle 1, using CTCAE v4. Results: A total of 22 pts (16m/6f) have been enrolled in 3 DLs: RO 625mg (4 pts), 1250mg (6), and 2500mg (12) IV every 2 weeks (q2w), each in combination with BV 10mg/kg IV q2w. Median age: 58 years (range 37-72). RO serum concentrations increased proportionally, while serum exposures of BV were similar between all DLs. Two pts experienced a DLT: Meningitis G3 (1250 mg) and cerebral infarction G3 (2500 mg). Most commonly reported adverse events included hypertension (14 pts), headache (11), dysphonia (10), fatigue (6), nasopharyngitis (5), epistaxis (4), constipation (4), nausea (3), and arthralgia (3). Across all DLs tested, the overall response rate by RANO criteria was 22.7%. Conclusions: The tolerability of RO in combination with BV is acceptable; a MTD was not determined. Anti-PlGF treatment does not appear to add on clinical activity observed for single agent BV in recurrent GBM. Clinical trial information: NCT01308684.

Mitomycin C pharmacokinetics in patients with recurrent or metastatic colorectal carcinoma

1987 ◽  
Vol 65 (3) ◽  
pp. 407-411 ◽  
Author(s):  
Charles Erlichman ◽  
A. Michael Rauth ◽  
Rena Battistella ◽  
Sheldon Fine
Keyword(s):  
Colorectal Carcinoma ◽  
Mitomycin C ◽  
High Performance ◽  
Single Agent ◽  
Area Under The Curve ◽  
Metastatic Colorectal Carcinoma ◽  
Active Metabolites ◽  
Small Component ◽  
Drug Concentrations ◽  
Hplc Technique

The pharmacokinetics of mitomycin C as a single agent have been determined in 25 treatment courses given to 18 patients with recurrent or metastatic colorectal carcinoma using a high performance liquid chromatography (HPLC) assay to analyze plasma and urine samples. The plasma pharmacokinetics conformed to a two-compartment linear model in 21 of 25 courses monitored with a mean t½λ1 of 9.8 ± 1.2 (SEM) min and mean t½λz of 64.1 ± 8.9 (SEM) min. The large variation observed in t½λz was not related to dose or treatment, but an interaction of these two factors approached significance (p = 0.057). Renal excretion in the 12 courses in which it was determined averaged only 2.3% of the total administered dose during the first 4 h monitored and no mitomycin C metabolites were detected in plasma or urine by the HPLC technique used. The most common toxicity, thrombocytopenia, did not correlate with t½λz or the area under the curve. This may be due to (i) a failure to monitor active metabolites of mitomycin C; (ii) other factors besides plasma drug concentrations that mediate toxicity towards marrow elements; or (iii) the small number of courses associated with thrombocytopenia (<100 000/mm3). Our study indicates that (i) an interaction of drug dose and treatment course may be associated with increasing t½λz; (ii) the renal clearance contributes a small component of mitomycin C elimination; (iii) metabolites of mitomycin C cannot be detected by the present HPLC technique; and (iv) routine monitoring of mitomycin C using present methods cannot be recommended for clinical use to predict toxicity.

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