Completion Rate Of Protocol Treatment Research Articles

Pre- versus postoperative CAPOX plus bevacizumab (CAPOX-Bev) for resectable liver metastases from colorectal cancer (CLM): A randomized phase II/III trial (HiSCO-01).

4021 Background: The role of neoadjuvant chemotherapy, particularly for those with initially resectable CLM, is controversial. And the optimal regimen and duration to be used in the neoadjuvant setting is not established. We conducted prospective, multicenter, randomized phase II/III study to assess pre-operative 8 cycles of CAPOX-Bev (arm A) plus radical surgery compared with post-operative 8 cycles of CAPOX-Bev (arm B) for patients (pts) with resectable CLM. Methods: The primary endpoint in the Phase II was completion rate of protocol treatment (more than 6 cycles of CAPOX-Bev plus R0 surgical resection) and PFS in the Phase III. The secondary endpoints were OS, ORR (arm A), liver damage (arm A), safety. The Phase III part was terminated due to slow enrollment. Results: 81 pts were enrolled from 10 centers between November 2010 and November 2017. The full analysis set consisted of 76 pts who started protocol treatment (arm A 37 vs. arm B 39). 76 pts had the following characteristics: median age 66 (27-80), median number of liver metastases 2 (1-14), 69.7% male, 67.1% synchronous and 94.7% primary resected. Completion rate of protocol treatment was 89.2% in arm A and 71.8% in arm B (p = .06). ORR was 63.9%, including 2 pts who had pathologically complete response (5.6%). Only 1 pts in arm A could not undergo surgery due to progression of disease. In the chemotherapy safety population, arm B was associated with more grade 3 neutropenia and grade 3 gastrointestinal disorder than arm A. The most frequent surgical adverse event was biliary fistula, with an incidence of 0% in arm A and 10.3% in arm B (p = .02). No patient died from treatment-related adverse events. The median follow-up time was 40 months. The rate of PFS at 3 years was 32.2% in arm A versus 38.5% in arm B (p = .99). Conclusions: Pre-operative 8 cycles of CAPOX-Bev is compatible with radical surgery, but may have no impact on progression-free survival compared with post-operative chemotherapy. Clinical trial information: UMIN000003783 .

Survival results of hepatectomy followed by adjuvant chemotherapy with three months of capecitabine plus oxaliplatin for colorectal cancer liver metastases: A multicenter phase II study.

866 Background: Hepatic resection is one of the treatment strategies for resectable colorectal cancer liver metastases (CLM). The role of neoadjuvant and adjuvant chemotherapy in the management of initially resectable CLM is still unclear. Adjuvant chemotherapy consisting of capecitabine plus oxaliplatin (CapeOx) appears to be equivalent to FOLFOX in patients with stage III colon cancer. Furthermore, the IDEA collaboration reported that adjuvant chemotherapy with the three months of CapeOx after curative resection for stage III colon cancer has equivalent efficacy to adjuvant chemotherapy for 6 months. We conducted a multi-institutional, single-arm, phase II trial to confirm the feasibility of the three months of adjuvant CapeOx for post curative resection of CLM. Methods: Patients received one course of capecitabine followed by four courses of CapeOx for a total five courses (15 weeks) as adjuvant chemotherapy after curative resection of CLM. Oral capecitabine was given with 1,000 mg/m2 twice daily for 2 weeks in a 3-week cycle, and CapeOx consisted of oral capecitabine plus oxaliplatin 130 mg/m2 on day 1 in a 3-week cycle. The primary endpoint was completion rate of adjuvant chemotherapy. We set a threshold completion rate of protocol treatment of 45% and an expected completion rate of 70%. Given a one-sided α of 0.1 and statistical power of 80%, a minimum of 25 patients was required. Results: From May 2013 to November 2015, Twenty-eight patients were enrolled from six institutions: median age 69.5y, 54% male, 78.5% left-sided primary. Of the patients, 15 were synchronous metastases and 13 were metachronous. The locations of the metastases were unilobar in 20 patients and bilobar in 8. The mean number of lesions resected was two (range, 1 to 4). Among the 28 patients, 20 (71.4%: 95% CI, 53.6 to 89.3%) completed the protocol treatment. The most common grade 3/4 toxicities were neutropenia (29%). No treatment related death was observed. With a median follow-up period of 36 months (range 15-53months), 3 year-relapse free survival was 75.3%. Conclusions: The three months of adjuvant CapeOx is tolerable for post curative resection of CLM. Clinical trial information: 000011164.

Phase II trial of sorafenib combined with on-demand transarterial chemoembolization for advanced stage hepatocellular carcinoma (Barcelona Clinic Liver Cancer stage C): STAB study.

e15648 Background: Sorafenib has been acknowledged as a standard treatment for advanced stage hepatocellular carcinoma (HCC). This study was conducted to evaluate the safety and efficacy of combination therapy of sorafenib and on-demand transarterial chemoembolization (TACE) for advanced stage HCC. Methods: Inclusion criteria were advanced stage HCC (Barcelona Clinic Liver Cancer stage C), a systemic chemotherapy native status, an Eastern Cooperative Oncology Group performance status 0–1, and a Child-Pugh grade-A. Sorafenib therapy (800 mg daily) was started 4–28 days after TACE. On-demand TACE was allowed. The primary endpoint was the completion rate of protocol treatment, which was defined as sorafenib administration at least for 2 months from initial TACE. Secondary endpoints were objective response rate (ORR), disease control rate (DCR) based on modified Response Evaluation Criteria in Solid Tumors, overall survival (OS), progression-free survival (PFS), and the incidence of adverse events. Results: From July 2013 to September 2015, a total of 32 patients were registered from 9 institutions, but one patient was excluded because his tumor turned out to be combined hepatocellular carcinoma and cholangiocarcinoma. The protocol treatment was completed in 28 of 31 enrolled patients (90.3%, 28/31). The median treatment duration was 7.0 months (range 0.5–30) with the median number of TACE was 1 (range 1–4) and the median sorafenib dosage of 400 mg daily (range 154-800). The ORR and DCR were 77% and 90%, respectively. Median OS and PFS were 17.3 months [95% confidence interval (CI), 11.9–22.6] and 5.4 months (95% CI, 4.6–6.2), respectively. The most common grade-3 or -4 adverse events were increased aspartate aminotransferase (55%, 17/31), increased alanine aminotransferase (45% 14/31), and hypertension (23%, 7/31). Conclusions: Combination therapy of sorafenib and on-demand TACE was well tolerated and safe. Furthermore, this combination treatment may provide a survival benefit to patients with advanced stage HCC. Clinical trial information: UMIN000014213.

Phase II feasibility study of preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil for esophageal squamous cell carcinoma

The combination of docetaxel, cisplatin, and 5-fluorouracil (DCF) as preoperative treatment for esophageal squamous cell carcinoma (ESCC) has not been investigated. We carried out a multicenter phase II feasibility study of preoperative chemotherapy with DCF for ESCC. Patients with clinical stage II/III ESCC (International Union Against Cancer TNM classification system, 6th edition) were eligible. Chemotherapy consisted of i.v. docetaxel (70-75 mg/m(2)) and cisplatin (70-75 mg/m(2)) on day 1, and continuous infusion of fluorouracil (750 mg/m(2)/day) on days 1-5. Antibiotic prophylaxis on days 5-15 was mandatory. This regimen was repeated every 3 weeks with a maximum of three cycles allowed. After completion of chemotherapy, esophagectomy with extended lymphadenectomy was carried out. The primary endpoint was the completion rate of protocol treatment. Forty-two eligible patients were enrolled. During chemotherapy, the most common grade 3 or 4 toxicities were neutropenia (83%), anorexia (7%), and stomatitis (5%). Forty-one (98%) patients underwent surgery. The completion rate of protocol treatment was 90.5% (38/42). No treatment-related death was observed and the incidence of operative morbidity was tolerable. According to RECIST, the overall response rate after the completion of DCF was 64.3%. Pathological complete response was achieved in 17%. The estimated 2-year progression-free survival and overall survival were 74.5% and 88.0%, respectively. Although these data are preliminary, preoperative DCF was well tolerated. Antitumor activity was highly promising and warrants further investigation. This trial was registered with University Hospital Medical Information Network (no. UMIN000002396).

Phase I/II trial of induction chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) followed by concurrent chemoradiotherapy in locally advanced esophageal squamous cell carcinoma.

4074 Background: Standard of care for unresectable locally advanced esophageal squamous cell carcinoma (ESCC) is concurrent chemoradiotherapy (CRT). However, its survival remains limited. Neoadjuvant chemotherapy with docetaxel, cisplatin and 5-FU (DCF) demonstrated promising activity with pathological complete response (CR) of 22% for resectable stage II/III ESCC (Hara H et.al, ASCO 2012). This study was performed to assess the efficacy and safety of induction chemotherapy with DCF followed by CRT in patients with unresectable locally advanced ESCC. Methods: Eligibility criteria included clinically T4 and/or M1 lymph node (LYM) ESCC, PS 0-1, and 20-70 years old. Treatment consisted of docetaxel 70 mg/m2, cisplatin 70 mg/m2 on day 1 and fluorouracil 750 mg/m2 on days 1 to 5, repeated every 3 weeks for three cycles, followed by cisplatin 70 mg/m2 on days 64 and 92, and fluorouracil 700 mg/m2on days 64 to 67 and 92 to 95 concurrently with radiotherapy (60Gy in 30 fractions, 5 days/week). Results: From August 2009 to November 2011, 33 patients were enrolled.There were 16 pts with T4M0 disease, 13 with nonT4M1 LYM, and 4 with T4M1 LYM.Most grade 3 or 4 toxicities were neutropenia (66%), leukopenia (39%), anorexia (18%), dysphasia (12%), nausea (9%), febrile neutropenia (6%), and hyponatremia (6%) during induction chemotherapy. Most grade 3 or 4 toxicities were leukopenia (27%), neutropenia (20%), dysphasia (17%), anorexia (13%), esophagitis (13%), nausea (10%), and febrile neutropenia (3%) during CRT. No treatment related death was observed. The completion rate of protocol treatment was 88% (29/33). The overall response rate after completion of induction chemotherapy was 61%. Eleven pts (38%) achieved CR after completion of protocol treatment. With a median follow-up period of 14 months, 1y-PFS and 1y-OS are 38.5 and 78.6 %, respectively. Of a total of 33 patients, eighteen patients (55%) received secondary treatment. Conclusions: Induction chemotherapy with DCF followed by CRT in unresectable locally advanced ESCC was well tolerated. Although these data are preliminay, this approach warrants further evaluation. Clinical trial information: UMIN000003370.

WS10-4 - Feasibility Study of Neoadjuvant Chemoradiotherapy with Cisplatin Plus 5-Fluorouracil for Clinical Stage II/III Esophageal Squamous Cell Carcinoma

ABSTRACT Background Based on the JCOG 9907 trial results, neoadjuvant chemotherapy with cisplatin (CDDP) plus 5-fluorouracil (5-FU) is considered a standard treatment of stage II/III esophageal squamous cell carcinoma (ESCC) in Japan. However, patient survival remains unsatisfactory and neoadjuvant chemoradiotherapy (NeoCRT) may improve the outcome of stage II/III ESCC patients. We conducted a feasibility study of NeoCRT with CDDP plus 5-FU and elective nodal irradiation for stage II/III ESCC. Methods Eligibility criteria included clinical stage II/III (UICC 6th, non-T4) ESCC, PS 0-1, and age 20–75 years. Chemotherapy consisted of two courses of 5-FU infusion (1000 mg/m2, days 1–4) and a 2-h CDDP infusion (75 mg/m2, day 1), with a 4-week interval. Radiotherapy was concurrently administered to a total 41.4 Gy in 23 fractions for primary tumor, metastatic lymph nodes (LNs) and regional LNs. Esophagectomy with extensive lymphadenectomy (≥D2) was carried out 42–56 days after NeoCRT. The primary end point was the completion rate of NeoCRT and R0 resection. Results Thirty-three patients were enrolled, including 2 ineligibles. In 31 eligible patients, the median age was 63 years (range, 40–73); PS0/1: 19/12; cStage IIA/IIB/III: 2/10/19. The completion rate of protocol treatment was 93.5% (29/31). During CRT, the most common grade 3 or 4 toxic effects were leukopenia (65%), neutropenia (65%), anemia (13%), thrombocytopenia (13%), febrile neutropenia (13%), anorexia (16%), esophagitis (16%), hyponatremia (16%). One treatment-related death was observed. The incidence of operative morbidity was similar to that in previous studies but incidence of anastomotic leakage was observed more frequently (27%). According to RECIST, the overall response rate was 78% (14/18) after CRT. Pathological complete response was achieved in 42% (13/31). Conclusions NeoCRT was tolerable and active. The randomized, controlled trial compared with neoadjuvant chemotherapy is needed and we plan it.

Feasibility study of neoadjuvant chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) for clinical stage II/III esophageal squamous cell carcinoma.

95 Background: In JCOG 9907, neoadjuvant chemotherapy with cisplatin and 5-fluorouracil (CF) improved overall survival without additional serious adverse events in treating stage II/III esophageal squamous cell carcinoma (ESCC). However, ESCC patient survival remains unsatisfactory. We conducted a feasibility study of neoadjuvant chemotherapy with docetaxel plus CF (DCF) for clinical stage II/III ESCC. Methods: Eligibility criteria included clinical stage II/III (non-T4) ESCC, PS 0–1, and age 20–70 years. Chemotherapy consisted of a 1-h infusion of docetaxel at 70 mg/m2 and 2-h infusion of cisplatin at 70 mg/m2 (day 1), and continuous infusion of 5-FU 750 mg/m2 (days 1 to 5). Antibiotic prophylaxis on days 5 to 15 was mandatory. This regimen was repeated every 3 weeks (maximum 3 cycles) until unacceptable toxicity, patient refusal, or disease progression was observed. After chemotherapy completion, transthoracic esophagectomy with extended (> D2) lymphadenectomy was performed. The primary endpoint was the completion rate of protocol treatment. Results: From July 2009 to Feb 2010, 34 patients were enrolled, including 2 ineligibles. The 32 eligibles had a median age of 61 (range 36–70; male/female: 30/2), with PS0/1 of 20/12 and cStage IIA/IIB/III of 6/8/18. During chemotherapy, the most common grade-3 or -4 toxicities were neutropenia (88%), febrile neutropenia (3%), anorexia (9%), and stomatitis (6%). Thirty-one (97%) patients underwent surgery. The protocol completion rate was 87.5% (28/32). No treatment-related death was observed, and the operative morbidity incidence was comparable to those in previous studies. According to RECIST, the overall response rate was 61.5% after DCF completion. Primary-lesion pathological complete response was achieved in 26% of patients (8/31) who underwent esophagectomy. Conclusions: Neoadjuvant DCF was well tolerated. Although these data are preliminary, the protocol is highly promising and warrants further investigation. No significant financial relationships to disclose.