Abstract
Purpose: Preclinical studies have shown synergy between everolimus, an mTOR inhibitor, radiation, and platinum agents. We conducted a phase IB trial to determine the recommended phase II dose of everolimus with carboplatin and radiation. Materials and Methods: Patients with stage II/III esophageal cancer were enrolled. Following 2 cycles of Capecitabine/Oxaliplatin (XELOX), patients with no disease progression, received 50.4 Gy in 28 fractions and concurrent weekly carboplatin (area under the curve=2), with escalating doses of everolimus. A standard 3+3 dose escalation design was used. Results: Nineteen patients were enrolled. Two patients were screen failures and 4 were removed due to poor tolerance to XELOX (n=2) or disease progression (n=2). All treated patients had adenocarcinoma. Median age was 58 (44 to 71 y) and 85% were male patients. One patient at dose level 1 was replaced due to ongoing anxiety. One of 6 patients had a dose-limiting toxicity of bowel ischemia that was fatal. At dose level 2, two of 6 patients had a dose-limiting toxicity (fever with neutropenia and nausea). The recommended phase II dose of everolimus was 2.5 mg QOD. Grade ≥3 toxicities included lymphopenia (11%), nausea (10%), low white blood cell (8.0%) vomiting (5.5%), decreased neutrophils (4.0%). All patients achieved an R0 resection with a pathologic response rate of 40% and a pathologic complete response (ypCR) rate of 23%. The 2-year progression-free survival and overall survival were 50% and 49.6%, respectively. Conclusions: The recommended phase II dose of everolimus with concurrent weekly carboplatin and radiation is 2.5 mg QOD.
| Original language | English (US) |
|---|---|
| Journal | American Journal of Clinical Oncology: Cancer Clinical Trials |
| DOIs | |
| State | Published - Jan 1 2019 |
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Keywords
- everolimus in esophageal cancer
- mTOR and radiation
- mTOR in esophageal cancer
- radiation and everolimus
- XELOX and esophageal cancer
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Phase IB study of induction chemotherapy with XELOX, followed by radiation therapy, carboplatin, and everolimus in patients with locally advanced esophageal cancer. / Saba, Nabil F.; Force, Seth; Staley, Charley; Fernandez, Felix; Willingham, Field; Pickens, Allan; Cardona, Kenneth; Chen, Zhengjia; Goff, Laura; Cardin, Dana; Lambright, Eric; Nesbitt, Jon; Krasinskas, Alyssa; Higgins, Kristin; Harvey, R. Donald; Owonikoko, Taofeek; Ramalingam, Suresh S.; Shin, Dong M.; Beitler, Jonathan J.; El-Rayes, Bassel F.; Salaria, Safia; El-Rifai, Wael; Landry, Jerome; Chakravarthy, A. B.
In: American Journal of Clinical Oncology: Cancer Clinical Trials, 01.01.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Phase IB study of induction chemotherapy with XELOX, followed by radiation therapy, carboplatin, and everolimus in patients with locally advanced esophageal cancer
AU - Saba, Nabil F.
AU - Force, Seth
AU - Staley, Charley
AU - Fernandez, Felix
AU - Willingham, Field
AU - Pickens, Allan
AU - Cardona, Kenneth
AU - Chen, Zhengjia
AU - Goff, Laura
AU - Cardin, Dana
AU - Lambright, Eric
AU - Nesbitt, Jon
AU - Krasinskas, Alyssa
AU - Higgins, Kristin
AU - Harvey, R. Donald
AU - Owonikoko, Taofeek
AU - Ramalingam, Suresh S.
AU - Shin, Dong M.
AU - Beitler, Jonathan J.
AU - El-Rayes, Bassel F.
AU - Salaria, Safia
AU - El-Rifai, Wael
AU - Landry, Jerome
AU - Chakravarthy, A. B.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Purpose: Preclinical studies have shown synergy between everolimus, an mTOR inhibitor, radiation, and platinum agents. We conducted a phase IB trial to determine the recommended phase II dose of everolimus with carboplatin and radiation. Materials and Methods: Patients with stage II/III esophageal cancer were enrolled. Following 2 cycles of Capecitabine/Oxaliplatin (XELOX), patients with no disease progression, received 50.4 Gy in 28 fractions and concurrent weekly carboplatin (area under the curve=2), with escalating doses of everolimus. A standard 3+3 dose escalation design was used. Results: Nineteen patients were enrolled. Two patients were screen failures and 4 were removed due to poor tolerance to XELOX (n=2) or disease progression (n=2). All treated patients had adenocarcinoma. Median age was 58 (44 to 71 y) and 85% were male patients. One patient at dose level 1 was replaced due to ongoing anxiety. One of 6 patients had a dose-limiting toxicity of bowel ischemia that was fatal. At dose level 2, two of 6 patients had a dose-limiting toxicity (fever with neutropenia and nausea). The recommended phase II dose of everolimus was 2.5 mg QOD. Grade ≥3 toxicities included lymphopenia (11%), nausea (10%), low white blood cell (8.0%) vomiting (5.5%), decreased neutrophils (4.0%). All patients achieved an R0 resection with a pathologic response rate of 40% and a pathologic complete response (ypCR) rate of 23%. The 2-year progression-free survival and overall survival were 50% and 49.6%, respectively. Conclusions: The recommended phase II dose of everolimus with concurrent weekly carboplatin and radiation is 2.5 mg QOD.
AB - Purpose: Preclinical studies have shown synergy between everolimus, an mTOR inhibitor, radiation, and platinum agents. We conducted a phase IB trial to determine the recommended phase II dose of everolimus with carboplatin and radiation. Materials and Methods: Patients with stage II/III esophageal cancer were enrolled. Following 2 cycles of Capecitabine/Oxaliplatin (XELOX), patients with no disease progression, received 50.4 Gy in 28 fractions and concurrent weekly carboplatin (area under the curve=2), with escalating doses of everolimus. A standard 3+3 dose escalation design was used. Results: Nineteen patients were enrolled. Two patients were screen failures and 4 were removed due to poor tolerance to XELOX (n=2) or disease progression (n=2). All treated patients had adenocarcinoma. Median age was 58 (44 to 71 y) and 85% were male patients. One patient at dose level 1 was replaced due to ongoing anxiety. One of 6 patients had a dose-limiting toxicity of bowel ischemia that was fatal. At dose level 2, two of 6 patients had a dose-limiting toxicity (fever with neutropenia and nausea). The recommended phase II dose of everolimus was 2.5 mg QOD. Grade ≥3 toxicities included lymphopenia (11%), nausea (10%), low white blood cell (8.0%) vomiting (5.5%), decreased neutrophils (4.0%). All patients achieved an R0 resection with a pathologic response rate of 40% and a pathologic complete response (ypCR) rate of 23%. The 2-year progression-free survival and overall survival were 50% and 49.6%, respectively. Conclusions: The recommended phase II dose of everolimus with concurrent weekly carboplatin and radiation is 2.5 mg QOD.
KW - everolimus in esophageal cancer
KW - mTOR and radiation
KW - mTOR in esophageal cancer
KW - radiation and everolimus
KW - XELOX and esophageal cancer
UR - http://www.scopus.com/inward/record.url?scp=85061913907&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85061913907&partnerID=8YFLogxK
U2 - 10.1097/COC.0000000000000524
DO - 10.1097/COC.0000000000000524
M3 - Article
C2 - 30789414
AN - SCOPUS:85061913907
JO - American Journal of Clinical Oncology
JF - American Journal of Clinical Oncology
SN - 0277-3732
ER -