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Phase 1 study of oral TAS-102 in patients with refractory metastatic colorectal cancer.

Bendell JC, Rosen LS, Mayer RJ, Goldman JW, Infante JR, Benedetti F, Lin D, Mizuguchi H, Zergebel C, Patel MR - Cancer Chemother. Pharmacol. (2015)

Bottom Line: Therefore, RD was identified as 35 mg/m(2) bid.TAS-102 has an acceptable safety profile and preliminary evidence of disease stabilization in Western patients with refractory mCRC.Results from a randomized phase 3 study have shown survival benefit with disease stabilization evidence in this population.

View Article: PubMed Central - PubMed

Affiliation: Sarah Cannon Research Institute/Tennessee Oncology, PLLC, 250 25th Avenue North, Suite 200, Nashville, TN, 37203, USA. jbendell@tnonc.com.

ABSTRACT

Purpose: To evaluate safety of TAS-102 administered twice daily (bid) on days 1-5 and 8-12 of a 4-week cycle, confirm feasibility of the Japanese recommended dose (RD), 35 mg/m(2), in Western patients with metastatic colorectal cancer (mCRC) refractory to standard chemotherapies, and describe preliminary antitumor activity.

Methods: This open-label, dose-escalation phase 1 study was conducted at four US centers. Patients were enrolled into two sequential cohorts [30 (cohort 1) or 35 mg/m(2)/dose bid (cohort 2)]; dose-limiting toxicities (DLT) were evaluated during cycle 1 in dose-escalation cohorts. At RD, 15 additional patients were enrolled in an expansion cohort.

Results: Patients (N = 27) with refractory mCRC received TAS-102; 74 % had received ≥4 prior regimens. DLT was not observed in three patients in cohort 1, and was in one out of nine patients in cohort 2 (grade 3 febrile neutropenia). Therefore, RD was identified as 35 mg/m(2) bid. At RD, fatigue (63 %), gastrointestinal disturbances and nausea (46 %), vomiting (46 %), and diarrhea (42 %) were common but rarely grade 3/4. Grade 3/4 nausea, vomiting, and diarrhea occurred at 4 % each. Grade 3/4 toxicity was predominantly hematologic [neutropenia (71 %), anemia (25 %)]; febrile neutropenia was observed in two patients. Stable disease lasting ≥6 weeks was achieved by 16 evaluable patients (70 %); median progression-free survival and overall survival were 5.3 and 7.5 months, respectively.

Conclusions: TAS-102 has an acceptable safety profile and preliminary evidence of disease stabilization in Western patients with refractory mCRC. Results from a randomized phase 3 study have shown survival benefit with disease stabilization evidence in this population.

No MeSH data available.


Related in: MedlinePlus

Patient disposition
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Fig1: Patient disposition

Mentions: A total of 27 patients received TAS-102, including three patients in cohort 1 (30 mg/m2/dose twice daily), nine patients in cohort 2 (35 mg/m2/dose twice daily), and 15 patients in the expansion cohort (35 mg/m2/dose twice daily) (Fig. 1). All treated patients from cohorts 1 and 2 were included in the DLT evaluable population, and all patients were included in the safety evaluation. One patient without any post-baseline tumor assessments was excluded from the efficacy evaluation. At the time of data cutoff, one patient in the expansion cohort remained on TAS-102 treatment. Most patients discontinued study treatment due to radiologic progression.Fig. 1


Phase 1 study of oral TAS-102 in patients with refractory metastatic colorectal cancer.

Bendell JC, Rosen LS, Mayer RJ, Goldman JW, Infante JR, Benedetti F, Lin D, Mizuguchi H, Zergebel C, Patel MR - Cancer Chemother. Pharmacol. (2015)

Patient disposition
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4612319&req=5

Fig1: Patient disposition
Mentions: A total of 27 patients received TAS-102, including three patients in cohort 1 (30 mg/m2/dose twice daily), nine patients in cohort 2 (35 mg/m2/dose twice daily), and 15 patients in the expansion cohort (35 mg/m2/dose twice daily) (Fig. 1). All treated patients from cohorts 1 and 2 were included in the DLT evaluable population, and all patients were included in the safety evaluation. One patient without any post-baseline tumor assessments was excluded from the efficacy evaluation. At the time of data cutoff, one patient in the expansion cohort remained on TAS-102 treatment. Most patients discontinued study treatment due to radiologic progression.Fig. 1

Bottom Line: Therefore, RD was identified as 35 mg/m(2) bid.TAS-102 has an acceptable safety profile and preliminary evidence of disease stabilization in Western patients with refractory mCRC.Results from a randomized phase 3 study have shown survival benefit with disease stabilization evidence in this population.

View Article: PubMed Central - PubMed

Affiliation: Sarah Cannon Research Institute/Tennessee Oncology, PLLC, 250 25th Avenue North, Suite 200, Nashville, TN, 37203, USA. jbendell@tnonc.com.

ABSTRACT

Purpose: To evaluate safety of TAS-102 administered twice daily (bid) on days 1-5 and 8-12 of a 4-week cycle, confirm feasibility of the Japanese recommended dose (RD), 35 mg/m(2), in Western patients with metastatic colorectal cancer (mCRC) refractory to standard chemotherapies, and describe preliminary antitumor activity.

Methods: This open-label, dose-escalation phase 1 study was conducted at four US centers. Patients were enrolled into two sequential cohorts [30 (cohort 1) or 35 mg/m(2)/dose bid (cohort 2)]; dose-limiting toxicities (DLT) were evaluated during cycle 1 in dose-escalation cohorts. At RD, 15 additional patients were enrolled in an expansion cohort.

Results: Patients (N = 27) with refractory mCRC received TAS-102; 74 % had received ≥4 prior regimens. DLT was not observed in three patients in cohort 1, and was in one out of nine patients in cohort 2 (grade 3 febrile neutropenia). Therefore, RD was identified as 35 mg/m(2) bid. At RD, fatigue (63 %), gastrointestinal disturbances and nausea (46 %), vomiting (46 %), and diarrhea (42 %) were common but rarely grade 3/4. Grade 3/4 nausea, vomiting, and diarrhea occurred at 4 % each. Grade 3/4 toxicity was predominantly hematologic [neutropenia (71 %), anemia (25 %)]; febrile neutropenia was observed in two patients. Stable disease lasting ≥6 weeks was achieved by 16 evaluable patients (70 %); median progression-free survival and overall survival were 5.3 and 7.5 months, respectively.

Conclusions: TAS-102 has an acceptable safety profile and preliminary evidence of disease stabilization in Western patients with refractory mCRC. Results from a randomized phase 3 study have shown survival benefit with disease stabilization evidence in this population.

No MeSH data available.


Related in: MedlinePlus