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The retrospective analysis of gemcitabine+nab-paclitaxel for the treatment of advanced pancreatic cancer
Abstracts / Pancreatology 16 (2016) S1eS192
Background: FOLFIRINOX is considered one of the standard chemotherapy regimens for chemotherapy-naïve pts. with MPC, but carries an unfavorable adverse event (AE) profile. Objective: The purpose of this study was to evaluate the efficacy and safety of modified FOLFIRINOX regimen: intravenous oxaliplatin 85 mg/ m2, irinotecan 150 mg/m2, 5-FU infusion 2,400 mg/m2over 46 h, no bolus 5-FU. Methods: This study was an open-label, multicenter, single-arm phase II study. The primary endpoint was overall survival and the incidence of grade 3 or more neutropenia. All patients did not receive prophylactic pegfilgrastim. Results: Sixty-nine pts. were enrolled from 39 institutions in Japan. Median age was 62.6 years (range 42.4-74.2). All pts. had no prior treatment and had distant metastatic lesions. 68.1% of the pts. had a PS 0, the primary site of the tumor was the head of the pancreas in 44.9% of pts., 20.3% of pts. had a biliary stent, and 5.8% of pts. experienced recurrence after resection. The UGT1A1 genotype was wild type in 79.7%, heterozygous (*1/*6, *1/*28) in 20.3%. Median overall survival was 11.2 months (95% confidence interval [CI], 9.0-) and the 1-year survival proportion was 0.481. Median progression-free survival was 5.5 months (95% CI, 4.1-6.7). The response rate was 37.7% (95% CI, 26.3-50.2) and disease control rate was 78.3% (95% CI, 66.7-87.3). The incidence of grade 3 or more neutropenia was 47.8%. Other major grade 3 or more toxicities were febrile neutropenia (8.7%), thrombocytopenia (2.9%), anorexia (15.9%), diarrhea (10.1%), nausea (8.7%), cholangitis (5.8%) and peripheral sensory neuropathy (5.8%). Serious adverse events occurred in 6 pts. (8.7%). All AE proportions were less than those in the previous Japanese full dose Phase II study. One patient died due to interstitial pneumonia. Conclusions: Modified FOLFIRINOX of this study has an improved safety profile with maintained efficacy in MPC.
S8-4. Clinical outcome of gemcitabine and Nab-paclitaxel therapy in unresectable pancreatic cancer at high-volume cancer center institution Yusuke Hashimoto 1, Izumi Ono 1, Shuichi Mitsunaga 1, Hideaki Takahashi 1, Kazuo Watanabe 1, Kumiko Umemoto 1, Akira Kobayashi 2, Misaki Kobayashi 2, Ai Irisawa 2, Yuko Asanagi 2, Masahumi Ikeda 1 1 Hepatobiliary and Pancreatic Oncology, National Cancer Center East Hospital, Japan 2 Pharmacy Division, National Cancer Center East Hospital, Japan
Backgound: Gemcitabine (GEM) and Nab-Paclitaxel (Nab-PTX) therapy represents optimal first line therapeutic option in metastatic pancreatic cancer (PC). Japanese phaseI/II trial in metastatic PC has demonstrated high overall response rate 58.5%, PFS 6.5 months and OS 13.5 months. Advanced PC converted to resectable status by use of chemotherapy with good tumor response may improve patient survival. We show our short period clinical outcome with surgical conversion cases presentation at a single cancer center after Nab-PTX obtained approval in Dec 2014 in Japan. Method: Clinical medical records of PC patients receiving GEM 1000 mg/m2 and Nab-PTX 125 mg/m2 on days 1,8 and 15 of a 28 day cycle as were retrospectively reviewed. Results: We have treated 179 unresectable PC patients between December 2014 and October 2015. 103 patients (M/F: 63/40), median age 64 (range 37-80), ECOG Performance Status of 0/1/2: 73/29/1, Head/body/ Tail: 51/36/16,UICC 3/4: 26/77,16 prior surgical resection, respectively were evaluated on tumor response and included in our analysis. 12 patients (12%) were75 years old. 0 complete and 51 partial responses were observed with 48.5% response rate and 91.2% disease control rate. CA19-9 decrease was seen in 80% patients. Over 50% tumor shrinkage was seen in 9 patients (8.7%). 3 of patients (UICC3/4: 2: 1) who received GEM and Nab-PTX (median 7: 6-9 cycle) and achieved good tumor response (median shrinkage: 55%: 44-88) were able to convert to surgical resection. Grade3/4 toxicity were 3 anorexia (2.9%), 1 diarrhea (0.9%), 44 neutropenia (42%), 7 thrombocytopenia (6.7%), 1 febrile neutropenia (0.9%), 6 peripheral neuropathy (5.8%), 2 peumonitis (1.9%) .
S31
Conclusion: We demonstrated a promising tumor response by GEM and Nab-PTX therapy and achieved successful conversion of 3 advanced PC patients. This study may highlight dawn breaking of advanced PC treatment.
S8-5. The retrospective analysis of gemcitabine+nab-paclitaxel for the treatment of advanced pancreatic cancer Makoto Ueno, Satoshi Kobayashi, Shinichi Ohkawa, Shun Tezuka, Satoshi Moriya, Manabu Morimoto Department of Gastroenterology, Hepatobiliary and Pancreatic Division, Kanagawa Cancer Center, Japan Background: Gemcitabine+nab-paclitaxel is one of the standard chemotherapies to treat advanced pancreatic cancer (APC). In Japan, it was approved for clinical use in December 2014. We performed gemcitabine+nab-paclitaxel in various lines in practice. Here, we examined the results of this treatment retrospectively in APC patients. Methods: The subjects were 92 APC patients. They were treated with gemcitabine+nab-paclitaxel starting from Dec. 2014 to July 2015. Both gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2) were administered on days 1, 8, and 15 for every 4 weeks. UICC stage, sex, age, performance status, Grade3/4 adverse effect and antitumor effect based on RECIST criteria (v1.1) were examined. Progression-free survival and overall survival were analized by Kaplan-Meier method. We compared the 1st line with the 2nd to 4th lines. Results: UICC stages were as follows; stage III: 17, stage IV: 61, and recurrence: 15. There were 54 males and 38 females, and their ages ranged from 44 to 83 years old (median: 67). The performance status was as follows; 0: 41, 1: 48, 2: 3. The treatment line was as follows; 1st: 57, 2nd: 15, 3rd: 15, 4th: 5. The febrile neutropenia was seen in only 2 patients (2%). The disease control rate (DCR) (PR+SD) was follows; 1st: 82%, other lines: 66%. The DCR was 78% in FOLFIRINOX refractory patients and 64% in gemcitabine refractory patients. Median PFS and OS were follows; in the 1st line: 5.7mo and 8.1mo, in the other lines: 2.3mo and 8.5mo. Grade 3/4 neutorophil count decreased; 58% in the 1st line, anemia; 14% in the 1st line and 40% in the other lines. Conclusion: Gemcitabine+nab-paclitaxel was effective as a 1st line chemotherapy as well as other lines to treat APC in practice.
S8-6. Experience of gemcitabine plus nab-paclitaxel combination therapy in second line and beyond for unresectable progressive and metastatic pancreatic cancer Hideki Takami, Tsutomu Fujii, Suguru Yamada, Tomonari Asano, Norimitsu Yabusaki, Mitsuro Kanda, Hiroyuki Sugimoto, Michitaka Fujiwara, Yasuhiro Kodera Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Japan Background: Efficacy and safety of gemcitabine (GEM) plus nabpaclitaxel (Nab-PTX) for unresectable progressive and metastatic pancreatic cancer in second line and beyond have not been clarified. Methods: We report a retrospective data analysis of 36 patients who received GEM plus Nab-PTX for unresectable progressive and metastatic pancreatic cancer at our department until December 2015. The patients were administered 125 mg/m2 Nab-PTX followed by 1000 mg/ m2 GEM on day 1, 8, and 15 every 4 weeks. They were classified into the first line group (group F) and the second line and beyond group (group S) and compared and examined about a patient background, the relative dose intensity (RDI), the adverse event frequency and the therapeutic effect.
Background: FOLFIRINOX is considered one of the standard chemotherapy regimens for chemotherapy-naïve pts. with MPC, but carries an unfavorable adverse event (AE) profile. Objective: The purpose of this study was to evaluate the efficacy and safety of modified FOLFIRINOX regimen: intravenous oxaliplatin 85 mg/ m2, irinotecan 150 mg/m2, 5-FU infusion 2,400 mg/m2over 46 h, no bolus 5-FU. Methods: This study was an open-label, multicenter, single-arm phase II study. The primary endpoint was overall survival and the incidence of grade 3 or more neutropenia. All patients did not receive prophylactic pegfilgrastim. Results: Sixty-nine pts. were enrolled from 39 institutions in Japan. Median age was 62.6 years (range 42.4-74.2). All pts. had no prior treatment and had distant metastatic lesions. 68.1% of the pts. had a PS 0, the primary site of the tumor was the head of the pancreas in 44.9% of pts., 20.3% of pts. had a biliary stent, and 5.8% of pts. experienced recurrence after resection. The UGT1A1 genotype was wild type in 79.7%, heterozygous (*1/*6, *1/*28) in 20.3%. Median overall survival was 11.2 months (95% confidence interval [CI], 9.0-) and the 1-year survival proportion was 0.481. Median progression-free survival was 5.5 months (95% CI, 4.1-6.7). The response rate was 37.7% (95% CI, 26.3-50.2) and disease control rate was 78.3% (95% CI, 66.7-87.3). The incidence of grade 3 or more neutropenia was 47.8%. Other major grade 3 or more toxicities were febrile neutropenia (8.7%), thrombocytopenia (2.9%), anorexia (15.9%), diarrhea (10.1%), nausea (8.7%), cholangitis (5.8%) and peripheral sensory neuropathy (5.8%). Serious adverse events occurred in 6 pts. (8.7%). All AE proportions were less than those in the previous Japanese full dose Phase II study. One patient died due to interstitial pneumonia. Conclusions: Modified FOLFIRINOX of this study has an improved safety profile with maintained efficacy in MPC.
S8-4. Clinical outcome of gemcitabine and Nab-paclitaxel therapy in unresectable pancreatic cancer at high-volume cancer center institution Yusuke Hashimoto 1, Izumi Ono 1, Shuichi Mitsunaga 1, Hideaki Takahashi 1, Kazuo Watanabe 1, Kumiko Umemoto 1, Akira Kobayashi 2, Misaki Kobayashi 2, Ai Irisawa 2, Yuko Asanagi 2, Masahumi Ikeda 1 1 Hepatobiliary and Pancreatic Oncology, National Cancer Center East Hospital, Japan 2 Pharmacy Division, National Cancer Center East Hospital, Japan
Backgound: Gemcitabine (GEM) and Nab-Paclitaxel (Nab-PTX) therapy represents optimal first line therapeutic option in metastatic pancreatic cancer (PC). Japanese phaseI/II trial in metastatic PC has demonstrated high overall response rate 58.5%, PFS 6.5 months and OS 13.5 months. Advanced PC converted to resectable status by use of chemotherapy with good tumor response may improve patient survival. We show our short period clinical outcome with surgical conversion cases presentation at a single cancer center after Nab-PTX obtained approval in Dec 2014 in Japan. Method: Clinical medical records of PC patients receiving GEM 1000 mg/m2 and Nab-PTX 125 mg/m2 on days 1,8 and 15 of a 28 day cycle as were retrospectively reviewed. Results: We have treated 179 unresectable PC patients between December 2014 and October 2015. 103 patients (M/F: 63/40), median age 64 (range 37-80), ECOG Performance Status of 0/1/2: 73/29/1, Head/body/ Tail: 51/36/16,UICC 3/4: 26/77,16 prior surgical resection, respectively were evaluated on tumor response and included in our analysis. 12 patients (12%) were75 years old. 0 complete and 51 partial responses were observed with 48.5% response rate and 91.2% disease control rate. CA19-9 decrease was seen in 80% patients. Over 50% tumor shrinkage was seen in 9 patients (8.7%). 3 of patients (UICC3/4: 2: 1) who received GEM and Nab-PTX (median 7: 6-9 cycle) and achieved good tumor response (median shrinkage: 55%: 44-88) were able to convert to surgical resection. Grade3/4 toxicity were 3 anorexia (2.9%), 1 diarrhea (0.9%), 44 neutropenia (42%), 7 thrombocytopenia (6.7%), 1 febrile neutropenia (0.9%), 6 peripheral neuropathy (5.8%), 2 peumonitis (1.9%) .
S31
Conclusion: We demonstrated a promising tumor response by GEM and Nab-PTX therapy and achieved successful conversion of 3 advanced PC patients. This study may highlight dawn breaking of advanced PC treatment.
S8-5. The retrospective analysis of gemcitabine+nab-paclitaxel for the treatment of advanced pancreatic cancer Makoto Ueno, Satoshi Kobayashi, Shinichi Ohkawa, Shun Tezuka, Satoshi Moriya, Manabu Morimoto Department of Gastroenterology, Hepatobiliary and Pancreatic Division, Kanagawa Cancer Center, Japan Background: Gemcitabine+nab-paclitaxel is one of the standard chemotherapies to treat advanced pancreatic cancer (APC). In Japan, it was approved for clinical use in December 2014. We performed gemcitabine+nab-paclitaxel in various lines in practice. Here, we examined the results of this treatment retrospectively in APC patients. Methods: The subjects were 92 APC patients. They were treated with gemcitabine+nab-paclitaxel starting from Dec. 2014 to July 2015. Both gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2) were administered on days 1, 8, and 15 for every 4 weeks. UICC stage, sex, age, performance status, Grade3/4 adverse effect and antitumor effect based on RECIST criteria (v1.1) were examined. Progression-free survival and overall survival were analized by Kaplan-Meier method. We compared the 1st line with the 2nd to 4th lines. Results: UICC stages were as follows; stage III: 17, stage IV: 61, and recurrence: 15. There were 54 males and 38 females, and their ages ranged from 44 to 83 years old (median: 67). The performance status was as follows; 0: 41, 1: 48, 2: 3. The treatment line was as follows; 1st: 57, 2nd: 15, 3rd: 15, 4th: 5. The febrile neutropenia was seen in only 2 patients (2%). The disease control rate (DCR) (PR+SD) was follows; 1st: 82%, other lines: 66%. The DCR was 78% in FOLFIRINOX refractory patients and 64% in gemcitabine refractory patients. Median PFS and OS were follows; in the 1st line: 5.7mo and 8.1mo, in the other lines: 2.3mo and 8.5mo. Grade 3/4 neutorophil count decreased; 58% in the 1st line, anemia; 14% in the 1st line and 40% in the other lines. Conclusion: Gemcitabine+nab-paclitaxel was effective as a 1st line chemotherapy as well as other lines to treat APC in practice.
S8-6. Experience of gemcitabine plus nab-paclitaxel combination therapy in second line and beyond for unresectable progressive and metastatic pancreatic cancer Hideki Takami, Tsutomu Fujii, Suguru Yamada, Tomonari Asano, Norimitsu Yabusaki, Mitsuro Kanda, Hiroyuki Sugimoto, Michitaka Fujiwara, Yasuhiro Kodera Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Japan Background: Efficacy and safety of gemcitabine (GEM) plus nabpaclitaxel (Nab-PTX) for unresectable progressive and metastatic pancreatic cancer in second line and beyond have not been clarified. Methods: We report a retrospective data analysis of 36 patients who received GEM plus Nab-PTX for unresectable progressive and metastatic pancreatic cancer at our department until December 2015. The patients were administered 125 mg/m2 Nab-PTX followed by 1000 mg/ m2 GEM on day 1, 8, and 15 every 4 weeks. They were classified into the first line group (group F) and the second line and beyond group (group S) and compared and examined about a patient background, the relative dose intensity (RDI), the adverse event frequency and the therapeutic effect.