- Email: [email protected]
oxaliplatin (SOX) for metastatic colorectal cancer (mCRC): JACCRO CC-06
abstracts
Annals of Oncology MO1 16 2
Update on phase II trial of cetuximab plus S-1/oxaliplatin (SOX) for metastatic colorectal cancer (mCRC): JACCRO CC-06
Background: We have determined the recommended dose of weekly cetuximab (cet) plus SOX (oxaliplatin 130mg/m2 on day 1 and S-1 40 mg/m2 twice daily on days 1-14, every 3 weeks) regimen and showed that it was an effective and tolerable 1st-line regimen in the JACCRO CC-06 trial for KRAS exon2 wild-type (wt) and EGFR-expressing mCRC [J Clin Oncol 2014 32:3_suppl, 571]. However, the follow-up time was short; therefore, the detailed data was missing. Methods: The primary endpoint of phase II part was objective response rate (ORR). Progression-free survival (PFS), overall survival (OS), early tumor shrinkage (ETS) at 8 weeks after treatment, depth of response (DpR), and safety were secondary endpoints. The tumor shrinkage was evaluated every 8 weeks by the external review board. Nonpreplanned updated analysis was performed in January 2019. Results: 59 pts (median 64-y old, 51% male, 85% PS0, 19% right-side) were enrolled into the phase II part. The median cycle of SOX was 6 (range 1-20) with relative dose intensity (RDI) of 80% for oxaliplatin and 83% for S-1. Cet was administered at median times of 17 (range 1-57), the RDI was 95%. Fifty-two (88%) pts discontinued the protocol therapy due to progression (46%) or toxicity (38%). The ORR was 62.7% (95%CI 50.4-75.1), median PFS was 9.1 months (95%CI 6.2-11.6), and median OS was 32.0 months (95%CI 21.5-44.2). In sub-analyses, pts with ETS had significantly longer PFS and OS compared to those without ETS (9.4 vs 3.8 months and 37.0 vs 22.5 months, respectively). Moreover, ETS rate and DpR were comparable between primary tumor sides (left vs. right, 70% vs 80%, 48% vs 46%, respectively). Exploratory analysis by RAS status indicated that ORR was 76.3%, median PFS was 9.4 months, and median OS was 32.0 months in RAS wt population (n ¼ 38). Conclusions: SOX plus cet regimen is active with good tumor shrinkage for KRAS wt mCRC regardless of primary tumor sidedness. Pts who experience ETS may potentially have a favorable prognosis.
MO1 17 2
Long-term results of a PII study of chemoradiotherapy with docetaxel, nedaplatin, and fluorouracil for esophageal cancer
Hiroyuki Ohnuma1, Naoki Onoyama1, Naotaka Hayasaka1, Masanori Sato1, Kazuyuki Murase1, Koichi Takada1, Koji Miyanishi1, Masahiro Hirakawa2, Tamotsu Sagawa2, Masakazu Hori3, Masanori Someya3, Kensei Nakata3, Koichi Sakata3, Junji Kato1 1 Department of Medical Oncology, Sapporo Medical University School of Medicine, 2 Division of Gastroenterology, Hokkaido Cancer Center, 3Department of Radiology, Sapporo Medical University School of Medicine Purpose: We previously reported early efficacy results from a phase I/II study of definitive chemoradiotherapy using docetaxel, nedaplatin and 5-fluorouracil (DNF-R), and confirmed strong antitumor activity with an acceptable early toxicity profile for patients with esophageal cancer. Here, we present the long-term results of the study including late toxicity and survival. Methods: Thirty-one patients were enrolled. Patients received 5-fluorouracil (400 mg/ m2 civ, d1-5 and d8-12), nedaplatin (50 mg/m2 on d1 and 8), and docetaxel (20-30 mg/ m2 on d1 and 8), repeated twice every 5 weeks with concurrent radiotherapy (59.4Gy/ 33fr). Study objectives in the phase II part included the CR rate, progression-free survival (PFS), overall survival (OS), and safety. Results: Between December 2008 and February 2014, a total of 28 patients were registered. Grade 3/4 acute toxicities included neutropenia (43%), febrile neutropenia (7%), thrombocytopenia (18%), and esophagitis (21%). Grade 3/4 late toxicity included esophagostenosis (11%) and pleural effusion (7%), though these resolved with dilation and thoracic drainage, respectively. All patients achieved a response, with 23 (82.1%) CR cases (stege II/III 89%, T4/M1LYM 67%). With a median follow-up time of 69.8 months, the 3-/5-year PFS and OS were 68.4/68.4% and 71.5/66.8%,
Volume 30 | Supplement 6 | October 2019
MO1 17 4
Efficacy and safety of early administration of pegfilgrastim for esophageal cancer treated with DCF: A phase 2 study
Tomoyo Yasuda1, Takeshi Ishikawa1,2, Osamu Dohi1, Tetsuya Okayama1, Naohisa Yoshida1, Kazuhiro Kamada1, Kazuhiko Uchiyama1, Osamu Handa1, Tomohisa Takagi1, Atsushi Shiozaki3, Hitoshi Fujiwara3, Hideyuki Konishi1, Yuji Naito1, Yoshito Itoh1 1 Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 2Outpatient Oncology Unit, University Hospital, Kyoto Prefectural University of Medicine, 3Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine Background: It has been reported that docetaxel, cisplatin and 5-fluorouracil (DCF) regimen was effective for advanced esophageal cancer. However, the DCF regimen is associated with a high risk of severe neutropenia or febrile neutropenia (FN). In our retrospective study evaluating the efficacy of pegfilgrastim administration on day 7 (D7) in DCF regimen, the neutrophil count nadir was observed from D7. Thus, the timing of its administration could be too late. In this study, we assess the efficacy and safety of early administration (D3) of pegfilgrastim in DCF therapy for advanced esophageal cancer. Methods: In this single-arm phase 2 study, patients with advanced esophageal cancer were recruited. They were treated with DCF therapy (DTX: 70mg/m2 on D1, CDDP: 70mg/m2 on D1, and 5-FU: 750mg/m2 on D1-5), and were administrated pegfilgrastim on D3. The primary endpoint was grade4 neutropenia. The secondary endpoints were the rate of FN and the incidence of other adverse events. This study was registered in UMIN system (UMIN000023393). Results: Between July 2016 and Dec. 2018, we enrolled 23 patients (median age 62y <44 - 75>). The incidence of grade4 neutropenia was 8.7% (95%CI:4.7 - 22.1). The rate of FN was 0%. The rate of grade3 neutropenia was 17.4% (95%CI: 1.7 - 33.1), but no other serious adverse events related to pegfilgrastim were observed. Conclusion: Primary prophylaxis with pegfilgrastim is recommended for the prevention of FN in patients receiving high-risk chemotherapy regimens such as DCF. According to the guidelines, G-CSF should be administered 24 h after the completion of chemotherapy. The optimal administration schedule remains unclear in regimens including IV continuous 5-FU administration like DCF. These results have shown that early administration (D3) of pegfilgrastim was safe and seemed to be more effective than D7 in DCF therapy. Further clinical studies with a larger sample size should be conducted to confirm our results.
MO1 17 5
Prognostic impact of serum inflammatory markers in oesophageal cancer following chemoradiation
Connie Yip1, Sze Huey Tan2, Michael Wang1, Tian Rui Siow1, Faye Lim1, Francis Chin1, Fuqiang Wang1, Shaun Ho1, Ni Sann Khin1 1 Radiation Oncology Department, National Cancer Centre Singapore, Singapore, 2 Clinical Trials and Epidemiological Sciences, National Cancer Centre Singapore Background: We compared the prognostic impact of various systemic inflammatory markers in oesophageal cancer. Methods: We retrospectively evaluated 77 patients treated with CRT for oesophageal cancer in a tertiary institution between 2006-2015. Baseline and post-CRT inflammatory parameters including haemoglobin, neutrophil, lymphocyte, platelet and albumin levels were recorded. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were derived. Primary end-point was overall survival (OS). Pre- and post-CRT values were compared using Wilcoxon Sign-Rank test. The prognostic ability of these parameters were evaluated using Cox regression analysis. Medians (IQRs) were presented. Bonferroni correction was applied; p < 0.005 was considered significant apart from multivariate analysis (p < 0.05) due to the small sample size. Results: Haemoglobin (-2 (-2.8,-0.8), p < 0.0001), neutrophil (-2.2 (-3.46,-0.29), p < 0.0001), lymphocyte (-0.9 (-1.30,-0.63), p < 0.0001), platelet (-41 (-132,22), p ¼ 0.001) and albumin (-2 (-6.5,1.0), p ¼ 0.0009) levels decreased after CRT. Both NLR (2.0 (-0.17,6.95), p < 0.0001) and PLR (201 (63,420), p < 0.0001) increased after treatment. Median OS was 20 months for all patients. Post-CRT NLR (HR 1.04, 95% CI 1.02-1.05, p < 0.001) and post-CRT PLR (HR 1.12, 95% CI 1.07-1.18, p < 0.001) were significant prognostic factors. No specific prognostic thresholds were identified. Advanced T-stage (HR 3.43, 95% CI 1.53-7.66, p ¼ 0.003) was also associated with inferior OS. In multivariate analysis, post-CRT NLR remains a significant prognostic factor (HR 1.03, 95% CI 1.01-1.06, p < 0.01). Conclusions: NLR and PLR may be more sensitive markers of systemic inflammatory milieu compared to individual serum indices which were all suppressed after CRT in oesophageal cancer. Systemic inflammatory status after CRT indicated by raised NLR/
doi:10.1093/annonc/mdz338 | vi97
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz338.029/5582862 by EKU Libraries user on 27 November 2019
Yu Sunakawa1, Wataru Ichikawa2, Ken Hagiwara3, Masahiro Tsuda4, Akinori Takagane5, Hisateru Yasui6, Hironaga Satake6, Tadamichi Denda7, Yoshihiko Segawa8, Hiroaki Tanioka9, Masahito Kotaka10, Mitsugu Kochi11, Takanori Watanabe12, Masato Nakamura13, Akihito Tsuji14, Satoshi Tani15, Yuji Negoro16, Kazutoshi Tobimatsu17, Masahiro Takeuchi18, Masashi Fujii19 1 Department of Clinical Oncology, St. Marianna University School of Medicine, 2 Division of Medical Oncology, Showa University Fujigaoka Hospital, 3Department of Digestive Surgery, Nihon University Hospital, 4Department of Gastroenterological Oncology, Hyogo Cancer Center, 5Department of Surgery, Hakodate Goryoukaku Hospital, 6Department of Medical Oncology, Kobe City Medical Center General Hospital, 7 Division of Gastroenterology, Chiba Cancer Center, 8Department of Medical Oncology, International Medical Center, Saitama Medical University, 9Department of Clinical Oncology, Kawasaki Medical School, 10Gastrointestinal center, Sano Hospital, 11 Department of Digestive Surgery, Nihon University Itabashi Hospital, 12Department of Surgery, Japanese Red Cross Society Himeji Hospital, 13Aizawa Comprehensive Cancer Center, Aizawa Hospital, 14Department of Medical Oncology, Kagawa University Hospital, 15Department of Internal Medicine, Kohnan Hospital, 16Department of Oncological Medicine, Kochi Health Sciences Center, 17Division of Gastroenterology, Kobe University Hospital, 18Department of Clinical Medicine (Biostatistics), Kitasato University School of Pharmacy, 19Department of Digestive Surgery, Nihon University School of Medicine
respectively. 5-year OS for stage II/III (nonT4) and T4/M1LYM were 68.4% and 28.6%, respectively. Conclusions: The long-term results show that efficacy was maintained with high rate of PFS and OS compared with those of historical control, with durable responses and acceptable safety profile. DNF-R might be a promising regimen for definitive CRT for esophageal cancer.
Annals of Oncology MO1 16 2
Update on phase II trial of cetuximab plus S-1/oxaliplatin (SOX) for metastatic colorectal cancer (mCRC): JACCRO CC-06
Background: We have determined the recommended dose of weekly cetuximab (cet) plus SOX (oxaliplatin 130mg/m2 on day 1 and S-1 40 mg/m2 twice daily on days 1-14, every 3 weeks) regimen and showed that it was an effective and tolerable 1st-line regimen in the JACCRO CC-06 trial for KRAS exon2 wild-type (wt) and EGFR-expressing mCRC [J Clin Oncol 2014 32:3_suppl, 571]. However, the follow-up time was short; therefore, the detailed data was missing. Methods: The primary endpoint of phase II part was objective response rate (ORR). Progression-free survival (PFS), overall survival (OS), early tumor shrinkage (ETS) at 8 weeks after treatment, depth of response (DpR), and safety were secondary endpoints. The tumor shrinkage was evaluated every 8 weeks by the external review board. Nonpreplanned updated analysis was performed in January 2019. Results: 59 pts (median 64-y old, 51% male, 85% PS0, 19% right-side) were enrolled into the phase II part. The median cycle of SOX was 6 (range 1-20) with relative dose intensity (RDI) of 80% for oxaliplatin and 83% for S-1. Cet was administered at median times of 17 (range 1-57), the RDI was 95%. Fifty-two (88%) pts discontinued the protocol therapy due to progression (46%) or toxicity (38%). The ORR was 62.7% (95%CI 50.4-75.1), median PFS was 9.1 months (95%CI 6.2-11.6), and median OS was 32.0 months (95%CI 21.5-44.2). In sub-analyses, pts with ETS had significantly longer PFS and OS compared to those without ETS (9.4 vs 3.8 months and 37.0 vs 22.5 months, respectively). Moreover, ETS rate and DpR were comparable between primary tumor sides (left vs. right, 70% vs 80%, 48% vs 46%, respectively). Exploratory analysis by RAS status indicated that ORR was 76.3%, median PFS was 9.4 months, and median OS was 32.0 months in RAS wt population (n ¼ 38). Conclusions: SOX plus cet regimen is active with good tumor shrinkage for KRAS wt mCRC regardless of primary tumor sidedness. Pts who experience ETS may potentially have a favorable prognosis.
MO1 17 2
Long-term results of a PII study of chemoradiotherapy with docetaxel, nedaplatin, and fluorouracil for esophageal cancer
Hiroyuki Ohnuma1, Naoki Onoyama1, Naotaka Hayasaka1, Masanori Sato1, Kazuyuki Murase1, Koichi Takada1, Koji Miyanishi1, Masahiro Hirakawa2, Tamotsu Sagawa2, Masakazu Hori3, Masanori Someya3, Kensei Nakata3, Koichi Sakata3, Junji Kato1 1 Department of Medical Oncology, Sapporo Medical University School of Medicine, 2 Division of Gastroenterology, Hokkaido Cancer Center, 3Department of Radiology, Sapporo Medical University School of Medicine Purpose: We previously reported early efficacy results from a phase I/II study of definitive chemoradiotherapy using docetaxel, nedaplatin and 5-fluorouracil (DNF-R), and confirmed strong antitumor activity with an acceptable early toxicity profile for patients with esophageal cancer. Here, we present the long-term results of the study including late toxicity and survival. Methods: Thirty-one patients were enrolled. Patients received 5-fluorouracil (400 mg/ m2 civ, d1-5 and d8-12), nedaplatin (50 mg/m2 on d1 and 8), and docetaxel (20-30 mg/ m2 on d1 and 8), repeated twice every 5 weeks with concurrent radiotherapy (59.4Gy/ 33fr). Study objectives in the phase II part included the CR rate, progression-free survival (PFS), overall survival (OS), and safety. Results: Between December 2008 and February 2014, a total of 28 patients were registered. Grade 3/4 acute toxicities included neutropenia (43%), febrile neutropenia (7%), thrombocytopenia (18%), and esophagitis (21%). Grade 3/4 late toxicity included esophagostenosis (11%) and pleural effusion (7%), though these resolved with dilation and thoracic drainage, respectively. All patients achieved a response, with 23 (82.1%) CR cases (stege II/III 89%, T4/M1LYM 67%). With a median follow-up time of 69.8 months, the 3-/5-year PFS and OS were 68.4/68.4% and 71.5/66.8%,
Volume 30 | Supplement 6 | October 2019
MO1 17 4
Efficacy and safety of early administration of pegfilgrastim for esophageal cancer treated with DCF: A phase 2 study
Tomoyo Yasuda1, Takeshi Ishikawa1,2, Osamu Dohi1, Tetsuya Okayama1, Naohisa Yoshida1, Kazuhiro Kamada1, Kazuhiko Uchiyama1, Osamu Handa1, Tomohisa Takagi1, Atsushi Shiozaki3, Hitoshi Fujiwara3, Hideyuki Konishi1, Yuji Naito1, Yoshito Itoh1 1 Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 2Outpatient Oncology Unit, University Hospital, Kyoto Prefectural University of Medicine, 3Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine Background: It has been reported that docetaxel, cisplatin and 5-fluorouracil (DCF) regimen was effective for advanced esophageal cancer. However, the DCF regimen is associated with a high risk of severe neutropenia or febrile neutropenia (FN). In our retrospective study evaluating the efficacy of pegfilgrastim administration on day 7 (D7) in DCF regimen, the neutrophil count nadir was observed from D7. Thus, the timing of its administration could be too late. In this study, we assess the efficacy and safety of early administration (D3) of pegfilgrastim in DCF therapy for advanced esophageal cancer. Methods: In this single-arm phase 2 study, patients with advanced esophageal cancer were recruited. They were treated with DCF therapy (DTX: 70mg/m2 on D1, CDDP: 70mg/m2 on D1, and 5-FU: 750mg/m2 on D1-5), and were administrated pegfilgrastim on D3. The primary endpoint was grade4 neutropenia. The secondary endpoints were the rate of FN and the incidence of other adverse events. This study was registered in UMIN system (UMIN000023393). Results: Between July 2016 and Dec. 2018, we enrolled 23 patients (median age 62y <44 - 75>). The incidence of grade4 neutropenia was 8.7% (95%CI:4.7 - 22.1). The rate of FN was 0%. The rate of grade3 neutropenia was 17.4% (95%CI: 1.7 - 33.1), but no other serious adverse events related to pegfilgrastim were observed. Conclusion: Primary prophylaxis with pegfilgrastim is recommended for the prevention of FN in patients receiving high-risk chemotherapy regimens such as DCF. According to the guidelines, G-CSF should be administered 24 h after the completion of chemotherapy. The optimal administration schedule remains unclear in regimens including IV continuous 5-FU administration like DCF. These results have shown that early administration (D3) of pegfilgrastim was safe and seemed to be more effective than D7 in DCF therapy. Further clinical studies with a larger sample size should be conducted to confirm our results.
MO1 17 5
Prognostic impact of serum inflammatory markers in oesophageal cancer following chemoradiation
Connie Yip1, Sze Huey Tan2, Michael Wang1, Tian Rui Siow1, Faye Lim1, Francis Chin1, Fuqiang Wang1, Shaun Ho1, Ni Sann Khin1 1 Radiation Oncology Department, National Cancer Centre Singapore, Singapore, 2 Clinical Trials and Epidemiological Sciences, National Cancer Centre Singapore Background: We compared the prognostic impact of various systemic inflammatory markers in oesophageal cancer. Methods: We retrospectively evaluated 77 patients treated with CRT for oesophageal cancer in a tertiary institution between 2006-2015. Baseline and post-CRT inflammatory parameters including haemoglobin, neutrophil, lymphocyte, platelet and albumin levels were recorded. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were derived. Primary end-point was overall survival (OS). Pre- and post-CRT values were compared using Wilcoxon Sign-Rank test. The prognostic ability of these parameters were evaluated using Cox regression analysis. Medians (IQRs) were presented. Bonferroni correction was applied; p < 0.005 was considered significant apart from multivariate analysis (p < 0.05) due to the small sample size. Results: Haemoglobin (-2 (-2.8,-0.8), p < 0.0001), neutrophil (-2.2 (-3.46,-0.29), p < 0.0001), lymphocyte (-0.9 (-1.30,-0.63), p < 0.0001), platelet (-41 (-132,22), p ¼ 0.001) and albumin (-2 (-6.5,1.0), p ¼ 0.0009) levels decreased after CRT. Both NLR (2.0 (-0.17,6.95), p < 0.0001) and PLR (201 (63,420), p < 0.0001) increased after treatment. Median OS was 20 months for all patients. Post-CRT NLR (HR 1.04, 95% CI 1.02-1.05, p < 0.001) and post-CRT PLR (HR 1.12, 95% CI 1.07-1.18, p < 0.001) were significant prognostic factors. No specific prognostic thresholds were identified. Advanced T-stage (HR 3.43, 95% CI 1.53-7.66, p ¼ 0.003) was also associated with inferior OS. In multivariate analysis, post-CRT NLR remains a significant prognostic factor (HR 1.03, 95% CI 1.01-1.06, p < 0.01). Conclusions: NLR and PLR may be more sensitive markers of systemic inflammatory milieu compared to individual serum indices which were all suppressed after CRT in oesophageal cancer. Systemic inflammatory status after CRT indicated by raised NLR/
doi:10.1093/annonc/mdz338 | vi97
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz338.029/5582862 by EKU Libraries user on 27 November 2019
Yu Sunakawa1, Wataru Ichikawa2, Ken Hagiwara3, Masahiro Tsuda4, Akinori Takagane5, Hisateru Yasui6, Hironaga Satake6, Tadamichi Denda7, Yoshihiko Segawa8, Hiroaki Tanioka9, Masahito Kotaka10, Mitsugu Kochi11, Takanori Watanabe12, Masato Nakamura13, Akihito Tsuji14, Satoshi Tani15, Yuji Negoro16, Kazutoshi Tobimatsu17, Masahiro Takeuchi18, Masashi Fujii19 1 Department of Clinical Oncology, St. Marianna University School of Medicine, 2 Division of Medical Oncology, Showa University Fujigaoka Hospital, 3Department of Digestive Surgery, Nihon University Hospital, 4Department of Gastroenterological Oncology, Hyogo Cancer Center, 5Department of Surgery, Hakodate Goryoukaku Hospital, 6Department of Medical Oncology, Kobe City Medical Center General Hospital, 7 Division of Gastroenterology, Chiba Cancer Center, 8Department of Medical Oncology, International Medical Center, Saitama Medical University, 9Department of Clinical Oncology, Kawasaki Medical School, 10Gastrointestinal center, Sano Hospital, 11 Department of Digestive Surgery, Nihon University Itabashi Hospital, 12Department of Surgery, Japanese Red Cross Society Himeji Hospital, 13Aizawa Comprehensive Cancer Center, Aizawa Hospital, 14Department of Medical Oncology, Kagawa University Hospital, 15Department of Internal Medicine, Kohnan Hospital, 16Department of Oncological Medicine, Kochi Health Sciences Center, 17Division of Gastroenterology, Kobe University Hospital, 18Department of Clinical Medicine (Biostatistics), Kitasato University School of Pharmacy, 19Department of Digestive Surgery, Nihon University School of Medicine
respectively. 5-year OS for stage II/III (nonT4) and T4/M1LYM were 68.4% and 28.6%, respectively. Conclusions: The long-term results show that efficacy was maintained with high rate of PFS and OS compared with those of historical control, with durable responses and acceptable safety profile. DNF-R might be a promising regimen for definitive CRT for esophageal cancer.