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1.
Markus Moehler Rolf Mahlberg Volker Heinemann Radka Obermannová Eugen Kubala Bohuslav Melichar Arndt Weinmann Paul Scigalla Marietta Tesařová Petr Janda Fabienne Hédouin-Biville Wasat Mansoor 《Gastric cancer》2017,20(2):358-367
Background
This phase I study investigated the safety and the maximum tolerated dose (MTD) of the oral fluoropyrimidine S-1 when combined with epirubicin and oxaliplatin (EOS).Methods
Patients aged ≥18 years with advanced or metastatic solid tumors were enrolled in a 3 + 3 design with S-1 dose escalation (two planned cohorts) performed according to the occurrence of dose-limiting toxicity (DLT). On day 1 of each 21-day cycle, patients received epirubicin 50 mg/m2 followed by oxaliplatin 130 mg/m2 (maximum 8 cycles) and then S-1 [20 mg/m2 (cohort 1) or 25 mg/m2 (cohort 2), twice daily]: first dose, evening of day 1; subsequent administration on days 2–14, twice daily; last dose, morning of day 15 (unlimited number of S-1 cycles). After protocol amendment, enrollment in a third cohort was restricted to patients with chemotherapy-naïve advanced or metastatic esophagogastric cancer.Results
DLT was reported for two of the five patients in cohort 2, defining 20 mg/m2 twice daily as the MTD of S-1 combined with epirubicin and oxaliplatin in heavily pretreated patients. Thirteen patients with chemotherapy-naïve advanced or metastatic esophagogastric cancer were subsequently enrolled and treated at an S-1 dose level of 25 mg/m2 twice daily; no DLTs were reported; median overall survival was 13.1 months. Of the 11 evaluable patients, three (27 %) had partial responses and seven (64 %) had stable disease. The safety profile was in line with expectations.Conclusions
The promising activity of EOS (S-1 dose level, 25 mg/m2 twice daily) and acceptable safety profile support further clinical development of this combination for the first-line treatment of patients with advanced or metastatic esophagogastric cancer.2.
Hyungwoo Cho Min-Hee Ryu Kyu-pyo Kim Baek-Yeol Ryoo Sook Ryun Park Bum Soo Kim In-Seob Lee Hee-Sung Kim Moon-Won Yoo Jeong Hwan Yook Seong Tae Oh Byung Sik Kim Yoon-Koo Kang 《Gastric cancer》2017,20(6):970-977
Background
This study was conducted to determine the recommended dose (RD) of intraperitoneal docetaxel (ID) in combination with systemic capecitabine and cisplatin (XP) and to evaluate its efficacy and safety at the RD in advanced gastric cancer (AGC) patients with peritoneal metastasis.Methods
AGC patients with peritoneal metastasis received XP ID, which consists of 937.5 mg/m2 of capecitabine twice daily on days 1–14, 60 mg/m2 of intravenous cisplatin on day 1, and intraperitoneal docetaxel at 3 different dose levels (60, 80, or 100 mg/m2) on day 1, every 3 weeks. In the phase I study, the standard 3 + 3 method was used to determine the RD of XP ID. In the phase II study, patients received RD of XP ID.Results
In the phase I study, ID 100 mg/m2 was chosen as the RD, with one dose-limiting toxicity (ileus) out of six patients. The 39 AGC patients enrolled in the phase II study received the RD of XP ID. The median progression-free survival was 11.0 months (95% CI 6.9–15.1), and median overall survival was 15.1 months (95% CI 9.1–21.1). The most frequent grade 3/4 adverse events were neutropenia (38.6%) and abdominal pain (30.8%). The incidence of abdominal pain cumulatively increased in the later treatment cycles.Conclusions
Our study indicated that XP ID was effective, with manageable toxicities, in AGC patients with peritoneal metastasis. As the cumulative incidence of abdominal pain was probably related to bowel irritation by ID, it might be necessary to modify the dose.3.
Norisuke Nakayama Kenji Ishido Keisho Chin Ken Nishimura Mizutomo Azuma Satoshi Matsusaka Yasuhiro Inokuchi Satoshi Tanabe Yosuke Kumekawa Wasaburo Koizumi 《Gastric cancer》2017,20(2):350-357
Background
In Japan, S-1, an oral fluoropyrimidine, plus cisplatin is a standard regimen for advanced gastric cancer, whereas nab-paclitaxel is a treatment option. We aimed to evaluate the tolerance, pharmacokinetics, safety, and clinical efficacy of S-1 combined with nab-paclitaxel in patients with advanced gastric cancer in a phase 1 study.Methods
The primary objective was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of S-1 plus nab-paclitaxel. The study was designed in accordance with a standard 3 + 3 method. Patients received 3-week cycles of treatment. S-1 was administered orally at 80 mg/m2 twice daily for 14 days, and nab-paclitaxel was administered as an intravenous infusion at 180, 220, or 260 mg/m2 on day 1 or 8.Results
Among the 16 patients enrolled, dose-limiting toxicity was observed in one patient at level 2a (S-1 80 mg/m2 twice daily plus nab-paclitaxel 220 mg/m2 on day 1). The MTD was not obtained, but the RD was established as level 3a (S-1 80 mg/m2 twice daily plus nab-paclitaxel 260 mg/m2 on day 1). The most common grade 3–4 toxicity was neutropenia (62.5 %). The overall response rate was 54.5 %. The pharmacokinetic profiles of coadministered S-1 and paclitaxel were comparable to those of nab-paclitaxel or S-1 alone.Conclusions
Based on the present results, the RD was determined as level 3a (S-1 80 mg/m2 twice daily plus nab-paclitaxel 260 mg/m2 on day 1). This combination therapy was well tolerated and showed antitumor efficacy in patients with advanced gastric cancer.4.
Chu Matsuda Michitaka Honda Chihiro Tanaka Mutsumi Fukunaga Keiichiro Ishibashi Yoshinori Munemoto Taishi Hata Hiroyuki Bando Mitsuru Oshiro Michiya Kobayashi Yukihiko Tokunaga Akitomo Fujii Naoki Nagata Koji Oba Hideyuki Mishima 《International journal of clinical oncology / Japan Society of Clinical Oncology》2016,21(3):566-572
Background
The aim of this multicenter, open-label, randomized phase II trial was to evaluate the efficacy of a dose-dense capecitabine and oxaliplatin (XELOX) regimen in patients with metastatic colorectal cancer (mCRC) for whom reintroduction of oxaliplatin had been planned as a third- or later-line regimen.Methods
The patients with mCRC who had received prior chemotherapy including oxaliplatin and were scheduled for reintroduction of oxaliplatin were randomized to capecitabine (1,000 mg/m2) twice daily on days 1–14 and oxaliplatin (130 mg/m2) on day 1 every 21 days (Q3W group) or capecitabine (2,000 mg/m2) twice daily on days 1–7 and oxaliplatin (85 mg/m2) on day 1 every 14 days (Q2W group). The primary endpoint was the time-to-treatment failure (TTF). Other endpoints included overall survival (OS), progression-free survival (PFS) and other adverse events (AEs).Results
A total of 46 patients were enrolled in the trial—22 patients were randomly assigned to the Q3W group and 23 to the Q2W group. The median TTF was 3.4 months in both groups (hazard ratio [HR] 1.053; p = 0.880). The median PFS and OS were 3.3 and 9.2 months in the Q2W group and 4.3 and 12.1 months in the Q3W group, respectively (HR 1.15; p = 0.153 and 0.672; p = 0.836). The most common grade 3?4 AEs in the Q3W and Q2W groups were fatigue (27.3 vs 21.7), neuropathy (9.1 vs 0 %) and diarrhea (9.1 vs 0 %), respectively.Conclusion
There was no significant inter-group difference in any of the efficacy and safety endpoints, including TTF, OS, RFS and AEs. The results of this clinical trial were convincingly negative.5.
Masaya Hattori Hiroshi Ishiguro Norikazu Masuda Akiyo Yoshimura Shoichiro Ohtani Hiroyuki Yasojima Satoshi Morita Shinji Ohno Hiroji Iwata 《Breast cancer (Tokyo, Japan)》2018,25(1):108-117
Background
Eribulin is a nontaxane microtubule inhibitor with activity in patients with metastatic breast cancer (MBC). We conducted a phase I dose-finding study of eribulin and capecitabine in patients with MBC pretreated with anthracycline and taxane.Methods
Women with MBC aged ≤70 years were enrolled. A 3 + 3 dose escalation design was used: level 0 dosing, eribulin (1.4 mg/m2 intravenously on days 1 and 8) plus capecitabine [825 mg/m2 orally twice daily (BID)]; 2-weeks-on, 1-week-off in a 21-day cycle. If there were no dose-limiting toxicities (DLTs), level 1 capecitabine dose was 1000 mg/m2 BID. The primary objective was to determine maximum tolerated dose, DLTs, and recommended dose (RD). Secondary objectives included pharmacokinetics, safety, and best overall response rate.Results
Nine women with MBC were enrolled; six at level 0, three at level 1. One patient had grade 4 DLTs at level 0 (serum creatinine 7.65 mg/dL and uric acid 13.4 mg/dL), considered associated with study drugs. Level 1 dosing was taken as the RD. Neutropenia was the most common ≥grade 3 toxicity. Pharmacokinetic parameters of eribulin were not influenced by co-administration of capecitabine. Of three patients in level 1, one achieved partial response and one had prolonged stable disease.Conclusion
Eribulin with capecitabine in the level 1 dosing schedule was associated with manageable toxicities and promising clinical activity. This combination is recommended for phase II investigation.6.
Nozomu Fuse Hideaki Bando Keisho Chin Seiji Ito Takaki Yoshikawa Akira Tsuburaya Masanori Terashima Yoshiyuki Kawashima Tetsu Fukunaga Masahiro Gotoh Yasunori Emi Kazuhiro Yoshida Eiji Oki Seiji Takahashi Hiroshi Kuriki Kumi Sato Mitsuru Sasako 《Gastric cancer》2017,20(2):332-340
Background
Adjuvant chemotherapy with XELOX (capecitabine plus oxaliplatin) has been shown to be beneficial following resection of gastric cancer in South Korean, Chinese, and Taiwanese patients. This phase II study (J-CLASSIC-PII) was undertaken to evaluate the feasibility of XELOX in Japanese patients with resected gastric cancer.Methods
Patients with stage II or III gastric cancer who underwent curative D2 gastrectomy received adjuvant XELOX (eight 3-week cycles of oral capecitabine, 1000 mg/m2 twice daily on days 1–14, plus intravenous oxaliplatin 130 mg/m2 on day 1). The primary endpoint was dose intensity. Secondary endpoints were safety, proportion of patients completing treatment, and 1-year disease-free survival (DFS) rate.Results
One hundred patients were enrolled, 76 of whom completed the study as planned. The mean dose intensity was 67.2 % (95 % CI, 61.9–72.5 %) for capecitabine and 73.4 % (95 % CI, 68.4–78.4 %) for oxaliplatin, which were higher than the predefined age-adjusted threshold values of 63.4 % and 69.4 %, respectively, and the study therefore met its primary endpoint. The 1-year DFS rate was 86 % (95 % CI, 77–91 %). No new safety signals were identified.Conclusions
The feasibility of adjuvant XELOX in Japanese patients with resected gastric cancer is similar to that observed in South Korean, Chinese, and Taiwanese patients in the Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer (CLASSIC) study. Based on findings from this study and the CLASSIC study, the XELOX regimen can be considered an adjuvant treatment option for Japanese gastric cancer patients who have undergone curative resection.7.
William H. Isacoff Howard A. Reber Rudolph Bedford William Hoos Lola Rahib Alexander Upfill-Brown Timothy Donahue O. Joe Hines 《Targeted oncology》2018,13(4):461-468
Background
Continuous-infusion 5-fluorouracil (5FU) and calcium leucovorin plus nab-paclitaxel and oxaliplatin have been shown to be active in patients with pancreatic cancer. As a protracted low-dose infusion, 5FU is antiangiogenic, and has synergy with bevacizumab. As shown in the treatment of breast cancer, bevacizumab and nab-paclitaxel are also synergetic.Objective
In this paper we retrospectively analyze the survival of 65 patients with advanced pancreatic cancer who were treated with low-dose continuous (metronomic) chemotherapy given in conjunction with conventional anti-VEGF therapy.Patients and Methods
Since July of 2008, we have treated 65 patients with 5FU (180 mg/m2/day × 14 days) via an ambulatory pump. Calcium leucovorin (20 mg/m2 IV), nab-paclitaxel (60 mg/m2) IV as a 30-min infusion, and oxaliplatin (50 mg/m2) IV as a 60-min infusion were given on days 1, 8, and 15. Bevacizumab (5 mg/kg) IV over 30 min was administered on days 1 and 15. Cycles were repeated every 28–35 days. There were 42 women and 23 men, and the median age was 59 years. Forty-six patients had stage IV disease.Results
The median survival was 19 months, with 82% of patients surviving 12 months or longer. The overall response rate was 49%. There were 28 patients who had received prior treatment, 15 of whom responded to therapy. Fifty-two patients had elevated CA 19-9 prior to treatment. Of these, 21 patients had 90% or greater reduction in CA 19-9 levels. This cohort had an objective response rate of 71% and a median survival of 27 months. Thirty patients stopped treatment due to disease progression, and an additional 22 stopped because of toxicity. One patient died while on therapy.Conclusions
This non-gemcitabine-based regimen resulted in higher response rates and better survival than what is commonly observed with therapy given at conventional dosing schedules. Low-dose continuous (metronomic therapy) cytotoxic chemotherapy combined with antiangiogenic therapy is safe and effective.8.
Vasilios Karavasilis Epaminontas Samantas Georgia-Angeliki Koliou Anna Kalogera-Fountzila George Pentheroudakis Ioannis Varthalitis Helena Linardou Grigorios Rallis Maria Skondra Georgios Papadopoulos George Papatsibas Joseph Sgouros Athina Goudopoulou Konstantine T. Kalogeras Christos Dervenis Dimitrios Pectasides George Fountzilas 《Targeted oncology》2018,13(6):715-724
Background
The prognosis of patients with advanced pancreatic cancer is dismal, and there is a need for novel and effective treatments.Objectives
Tο determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of a novel gemcitabine (G) and temsirolimus (T) combination (phase I) and estimate the 6-month progression-free survival (PFS) in patients treated with the T?+?G combination (phase II).Patients and Methods
Eligible patients with histologically confirmed inoperable or metastatic pancreatic carcinoma (MPC) were entered into the trial. G was given bi-weekly and T weekly in a 4-week cycle. The first dose level was set at G 800 mg/m2 and T 10 mg. G was escalated in increments of 200 mg/m2 and T in increments of 5 mg until DLT was reached, and the recommended dose was used for the phase II part.Results
Thirty patients were enrolled in the phase I component at the pre-planned six dose levels; one bilirubin DLT of grade III occurred at the first dose level. The MTD was established as the approved doses of both drugs. Fifty-five patients were entered into the phase II component. Median relative dose intensities administered in the first cycle were 0.75 for T and 0.99 for G. Grade 3-4 hematological toxicities were recorded in 87.3% of patients. The most common non-hematological adverse events were metabolic disorders (81.8%) followed by gastrointestinal disorders (63.6%). Median PFS was 2.69 months (95% CI 1.74-4.95) and median OS was 4.95 months (95% CI 3.54-6.85), while the 6-month PFS rate was 30.9%.Conclusions
Combination of G and T is feasible in patients with locally advanced or MPC with manageable side effects, but lacks clinical efficacy.The study was registered in the Australian New Zealand Clinical Trials Registry (ACTRN12611000643976).9.
Hyeong Su Kim Min-Hee Ryu Dae Young Zang Sook Ryun Park Boram Han Won Ki Kang Sun Young Rha Minkyu Jung Jin-Soo Kim Byung Woog Kang Kyung-Hee Lee Sang-Young Rho Jung Han Kim Kab Choong Kim Ji Woong Cho Dae Ro Choi Hyun Lim Ho Suk Kang Jae Seung Soh Min-Jeong Kim Jinwon Seo Yoon-Koo Kang 《Gastric cancer》2018,21(5):802-810
Background
Doublet chemotherapy of platinum and 5-fluorouracil is a standard first-line treatment for patients with unresectable gastric cancer. Although the addition of taxane or irinotecan to this regimen has yielded promising efficacy, its use has been limited due to severe toxicities. To overcome this limitation, we evaluated the efficacy and safety of the combination of irinotecan, oxaliplatin, and S-1 (OIS) for the treatment of advanced gastric cancer.Methods
Chemotherapy-naïve patients with pathologically proven advanced gastric adenocarcinoma were assessed for eligibility. Irinotecan (135 mg/m2) and oxaliplatin (65 mg/m2) were administered intravenously on day 1, and S-1 (80 mg/m2/day) was administered orally on days 1–7 of every 2-week cycle.Results
Forty-four patients (median age 57 years) were enrolled and all but one patient had a good performance status (ECOG 0 or 1). A total of 529 cycles were administered, with a median of 9.5 (range 1–31) cycles per patient. The overall response rate was 61.4% (95% confidence interval [CI] 46.6–74.3). The median progression-free survival and overall survival were 10.8 months (95% CI 7.6–14.0) and 15.4 months (95% CI 12.6–18.2), respectively. Major toxicities included grade 3/4 neutropenia (38.6%), febrile neutropenia (13.6%), abdominal pain (9.1%), and diarrhea (9.1%).Conclusion
These data suggest that the OIS regimen is effective and relatively well tolerated in patients with advanced gastric cancer. Given that all the patients treated, but one, had a good performance status, these results must be confirmed in a patient population more representative of regular clinical practice.Trial Registration
ClinicalTrials.gov Identifier: NCT02527785.10.
J. Chen T. Su Y. Lin B. Wang J. Li J. Pan C. Chen 《Clinical & translational oncology》2018,20(3):411-419
Purpose
This study was conducted to investigate the efficacy and toxicity of combination treatment with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy with paclitaxel plus different platinum agents in locally advanced esophageal squamous cell carcinoma (ESCC).Methods
This retrospective study enrolled 242 patients treated with paclitaxel (135 mg/m2) plus platinum regimens. According to the different platinum agents used, patients were classified into: cisplatin 80 mg/m2 (CP), nidaplatinum 80 mg/m2 (NP), lobaplatin 35 mg/m2 (LP), and oxaliplatin 135 mg m2 (OP) groups, and survival and toxicity rates between the four groups were compared. The median overall survival (OS) was 31.1 months.Results
No significant differences were observed among the CP, NP, LP, and OP groups with regard to 3-year survival rates (46.2, 56.4, 45.7, and 29.0%, respectively). A stratified analysis indicated that 3-year survival rates were significantly lower in the OP group. Renal toxicities and gastrointestinal reactions were more frequent in the CP group than in the other three groups. Three-year survival rates were similar among patients receiving 2, 3, or ≥4 cycles of chemotherapy (40.1, 49.5, and 50.8%, respectively). Multivariate analysis indicated that tumor volume and maximum diameter of metastatic lymph nodes might be independent prognostic factors.Conclusion
Paclitaxel plus nidaplatinum or lobaplatin is recommended in locally advanced ESCC due to their satisfying therapeutic effects and less toxicity. Tumor volume and maximum diameter of metastatic lymph nodes are independent prognostic factors in ESCC patients receiving IMRT and concurrent chemotherapy.11.
Hiroki Hara Shigenori Kadowaki Masako Asayama Akira Ooki Toko Yamada Takako Yoshii Kensei Yamaguchi 《International journal of clinical oncology / Japan Society of Clinical Oncology》2018,23(2):275-280
Background
There are few chemotherapeutic options for advanced gastric cancer with severe disseminated peritoneal metastases, which are usually accompanied by ascites. Bolus 5-fluorouracil (5-FU) plus leucovorin therapy has been widely used against gastrointestinal malignancies, with resulting mild toxicities.Methods
We retrospectively analyzed the efficacy and safety of first-line chemotherapy with bolus 5-FU plus l-leucovorin in 30 advanced gastric cancer patients who had massive ascites and/or inadequate oral intake. This therapy consisted of 5-FU (600 mg/m2 IV bolus) plus l-leucovorin (250 mg/m2 2-h IV infusion) administered on a 6 weeks on/2 weeks off schedule.Results
Among all the patients, 26 (87%) were unable to eat and 12 (40%) had massive ascites. Major grade 3 or 4 adverse events were neutropenia (17%), nausea (7%), fatigue (7%), and diarrhea (3%); no treatment-related deaths were observed. The median progression-free survival and overall survival (OS) were 2.4 months [95% confidence interval (CI), 0.6–4.1] and 6.0 months (95% CI, 2.1–9.9), respectively. Objective improvement in oral intake was seen in 7 patients (27%). Improvement in ascites occurred in 9 (39%) of 23 patients. In multivariate analyses, the presence of both massive ascites and inadequate oral intake was significantly associated with worse OS (hazard ratio, 5.25; 95% CI, 1.61–17.1). The median OS for patients (n = 22) without this factor was 7.2 months (95% CI, 4.2–10.3).Conclusion
Our study suggests that bolus 5-FU plus l-leucovorin therapy is feasible and has clinical activity as palliative therapy in patients with severe peritoneal metastases from gastric cancer.12.
Yosuke Kito Nozomu Machida Sadayuki Kawai Satoshi Hamauchi Takahiro Tsushima Akiko Todaka Tomoya Yokota Kentaro Yamazaki Akira Fukutomi Yusuke Onozawa Kunihiro Tsuji Hisashi Doyama Yutaka Haraguchi Koji Nakashima Kenji Kunieda Keisei Taku Keita Mori Hirofumi Yasui 《International journal of clinical oncology / Japan Society of Clinical Oncology》2018,23(6):1084-1089
Purpose
Although oxaliplatin 130 mg/m2 every 3 weeks was approved for advanced gastric cancer in Japan, data regarding S-1 plus oxaliplatin 130 mg/m2 (SOX130) are limited in Japanese patients with advanced gastric cancer. We investigated the feasibility and safety of SOX130 in Japanese patients with advanced gastric cancer.Methods
Patients with unresectable or recurrent gastric adenocarcinoma, no previous chemotherapy, and Eastern Cooperative Oncology Group Performance Status of 0–1 were treated with SOX130. The primary endpoint was the 3-cycle completion rate, defined as the proportion of patients who completed the first three cycles with ≥?80% relative dose intensity of oxaliplatin.Results
Twenty-five patients were enrolled from April 2015 to 2016. The 3-cycle completion rate was 72.0% (90% confidence interval: 53.8–86.1), which was higher than the predetermined threshold rate of 50%. With the median number of cycles being 6 (range, 1–19+), grade 3 or 4 adverse events occurred in 10 patients (40%). Major grade 3 adverse events were anorexia (24%), thrombocytopenia (16%), and neutropenia (12%). No febrile neutropenia or treatment-related deaths occurred. Among 12 patients with measurable lesions, the overall response rate was 58.3%. Median progression-free and overall survival were 5.7 months (95% confidence interval 2.9–8.5) and 13.1 months (95% confidence interval 7.4–19.0), respectively.Conclusion
Results indicated that SOX130 was feasible in Japanese patients with advanced gastric cancer.13.
Do patients with metastatic urothelial carcinoma benefit from docetaxel as second-line chemotherapy?
Purpose
To evaluate the efficacy and toxicity of docetaxel regimen as second-line after failure of a platinum-based chemotherapy.Methods
Between May 2005 and June 2008, we retrospectively analyzed the data of 22 patients who had evidence of disease progression after one prior platinum-based regimen for metastatic urothelial carcinoma. Patients were treated with two different docetaxel dose schedules: (1) docetaxel 60 mg/m2 every 21 days for unfit patients or (2) docetaxel 75 mg/m2 every 21 days for fit patients.Results
Median number of docetaxel cycles was three. Overall disease control rate was 18 %. Of the 22 patients, no patient achieved complete or partial response and four patients had stable disease. Median progression-free survival was 1.67 months and median overall survival was 3.12 months. Neutropenia was the most common adverse event.Conclusions
This study identifies that docetaxel as second-line chemotherapy has low activity and was associated with significant toxicity.14.
N. Kentepozidis P. Economopoulou Ch. Christofyllakis L. Chelis A. Polyzos N. Vardakis F. Koinis L. Vamvakas P. Katsaounis K. Kalbakis Ch. Nikolaou V. Georgoulias A. Kotsakis 《Clinical & translational oncology》2017,19(3):317-325
Background
Platinum-based chemotherapy is the standard front-line treatment for patients with advanced non-small cell lung cancer (NSCLC). However, non-platinum combinations of third-generation chemotherapeutic agents are considered an alternative therapeutic option for patients who cannot tolerate the toxic effects of platinum compounds. In this study, the efficacy and toxicity of the combination of irinotecan plus cisplatin (IC) was compared to pemetrexed plus cisplatin (PC) regimen, in platinum-naïve patients with advanced NSCLC, who had been previously treated with the combination of a taxane plus gemcitabine.Patients and methods
A total of 124 patients with locally advanced or metastatic NSCLC were randomly assigned to either irinotecan 110 mg/m2 on day 1 and 100 mg/m2 on day 8 plus cisplatin 80 mg/m2 on day 8 every 3 weeks (IC arm) or pemetrexed 500 mg/m2 plus cisplatin 80 mg/m2 on day 1 every 3 weeks (PC arm). The primary endpoint of the study was the overall response rate (ORR).Results
The ORR and median progression-free survival (PFS) in the IC arm were 18 % and 3.3 months, respectively, while in the PC arm were 19 % and 4.2 months (p = ns). Median overall survival (OS) was significantly higher in patients with PC (6.9 vs. 10.9; p = 0.013). PC regimen had a better toxicity profile compared to IC, with a statistically significant lower incidence of grade 3/4 neutropenia (3 vs. 31 %; p = 0.0001) and diarrhea (1.6 vs. 14.7 %, p = 0.018).Conclusions
In patients with advanced NSCLC pretreated with docetaxel/gemcitabine, the combination of pemetrexed/cisplatin is associated with increased OS and is better tolerated than the combination of irinotecan/cisplatin and should be considered as a valid therapeutic option for platinum-naive, previously treated patients.ClinicalTrials.gov Identifier
NCT00614965.15.
Hironaga Satake Akihito Tsuji Masato Nakamura Masaaki Ogawa Takeshi Kotake Yukimasa Hatachi Hisateru Yasui Akinori Takagane Yoshihiro Okita Kumi Nakamura Toshihide Onikubo Masahiro Takeuchi Masashi Fujii 《International journal of clinical oncology / Japan Society of Clinical Oncology》2018,23(3):490-496
Background
FOLFOXIRI is now regarded as the chemotherapy regimen that offers the best platform for the treatment of colorectal cancer. However, the safety and efficacy of FOLFOXIRI + panitumumab has not been demonstrated. We conducted a phase I study to determine the recommended dose of FOLFOXIRI + panitumumab as first-line treatment for RAS wild-type metastatic colorectal cancer (mCRC).Methods
Patients received combination therapy consisting of panitumumab (6 mg/kg on day 1) + FOLFOXIRI [irinotecan (CPT-11), oxaliplatin (L-OHP) 85 mg/m2, and folinate (LV) 200 mg/m2] on day 1, followed by fluorouracil (5-FU) 3200 mg/m2 infused as a 46-h continuous infusion starting on day 1) repeated every 2 weeks as first-line treatment of RAS wild-type mCRC patients. A decrease in CPT-11 dose was planned (started at level 1: CPT-11 165 mg/m2).Results
Seven patients were enrolled, and six were assessed for safety and efficacy. Maximum tolerated dose was not reached at level 1; all patients were treated at these levels. The common Grade 3 or 4 relevant toxicities were diarrhea (50%), hypokalemia (33%) and stomatitis (33%). No treatment-related deaths occurred. Of the six patients assessed four had partial response and the two others had stable disease; hence, the response rate was 66.7% (95% confidence interval 28.9–100%) and the disease control rate was 100%. Time to protocol treatment failure was 7.2 (1.4–7.3) months.Conclusion
The FOLFOXIRI + panitumumab chemotherapy regimen was well tolerated by our patients with mCRC and showed promising anti-tumor activity. The recommended phase II dose was determined to be the same as the standard doses of this regimen used worldwide.16.
Izumi Tachibana Yasumasa Nishimura Masahiro Inada Kohei Fukuda Kazuki Ishikawa Tatsuyuki Nishikawa Masaki Yokokawa Kiyoshi Nakamatsu Shuichi Kanamori Jin-ichi Hida 《International journal of clinical oncology / Japan Society of Clinical Oncology》2018,23(6):1121-1126
Background
Chemoradiotherapy (CRT) is a standard treatment for anal canal cancer although many patients with anal canal cancer undergo surgery in Japan. The efficacy of CRT for anal canal cancer was evaluated retrospectively.Methods
Medical charts of 13 patients with anal canal cancer treated by definitive CRT from October 2004 to May 2016 were reviewed. Twelve patients had squamous cell carcinoma and one had adeno-squamous carcinoma. PET/CT simulation was performed in nine patients. The median total dose was 59.4 Gy (range 57.6–63.4 Gy) with fractions of 1.8–2.0 Gy. Ten patients received chemotherapy with mitomycin C (10 mg/m2) and fluorouracil (5-FU) (800 mg/m2 over 4 days) in weeks 1 and 5, while two patients were treated with cisplatin (40 mg) and 5-FU (750 mg over 5 days) in weeks 1 and 5. One elderly patient received radiotherapy (RT) alone.Results
All 13 patients were alive after a median follow-up period of 102 months (range 16–121 months). Local failure only occurred in the patient with adeno-squamous cell carcinoma, while there was no loco-regional recurrence or distant metastasis in the other 12 patients. The 5-year loco-regional control rate (LRC) and 5-year overall survival rate (OS) were 92% and 100%, respectively. Acute toxicities of ≥?grade 3 were observed in six patients (46%), mainly being dermatitis around the anal verge, and late toxicity of ≥?grade 3 occurred in one patient.Conclusion
CRT for squamous cell carcinoma of the anal canal achieved good LRC and OS with acceptable toxicities.17.
Purpose
Several cytotoxic chemotherapy regimens are active against metastatic breast cancer; however, benefits are modest and overall prognosis remains limited. For anthracycline and taxane-pretreated metastatic breast cancer, there remains a relative paucity of therapies with significant activity. This Phase II study evaluated the combination of capecitabine and oxaliplatin (XELOX) among patients with metastatic breast cancer being treated in the first- or second-line setting.Methods
Patients received oxaliplatin 85 mg/m2 on days 1 and 15, and capecitabine 1,500 mg/m2 twice daily on days 1–7 and 15–21 of a 28-day cycle. Patients were treated until progression or intolerable toxicity. The primary objective was to estimate the objective response rate by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria with tumor assessments every 8 weeks.Results
Ten patients were treated of which 3 had received prior neurotoxic therapy in the metastatic setting. There were no confirmed complete responses, 5 patients had partial response, 4 patients had stable disease for at least 24 weeks, and one patient was unevaluable. Median time to progression (TTP) was 10.4 months (95 % lower confidence bound [LCB]: 5.75 months), median progression-free survival (PFS) was 14.2 months (95 % LCB: 6.14 months), and median overall survival (OS) was 19 months (95 % LCB: 12.8 months). Multiple patients experienced pain syndromes and unusual neuropathies. Other common toxicities included fatigue, diarrhea, and nausea.Conclusions
XELOX is a promising regimen for anthracycline-pretreated metastatic breast cancer although careful patient selection is indicated and alternate dosing schedules should be explored to minimize neurologic morbidity.18.
Mozaffar Aznab Omid Beiki Kiumars Eslam pia Khosro Setayeshi Mohamad Ali Hesami Houshang Vrae 《Journal of gastrointestinal cancer》2017,48(1):31-37
Aim
Our aim was to evaluate impact of chemotherapy (5-fluorouracil plus docetaxel and cisplatin) on the survival of gastric cancer cases.Method
Seventy-nine patients were eligible to take part in this study between November 2006 and April 2013, who received 5-fluorouracil (700 mg/m2, 21-h infusion within 5 days), cisplatin (60 mg/m2 on day 3), and Docetaxel (60 mg/m2 on day 2). Radiotherapy was added to the treatment only in the cases with entire stomach body cancer (positive margin) and with giant ulcer (above 50 mm) in proximal gastric cancer.Results
Twenty-four patients were female and 55 were male. The median age was 54. In this study, 54 % of the tumors were located in the proximal and 46 % in the distal of stomach. Seventy five percent of patients were at stage I–III (adjuvant chemotherapy), and 25 % at stage IV (palliative chemotherapy). Ninety-one percent of the patients at stages I–II, 68.3 % of the patients at stage III, and one out of 20 patients at stage IV were alive at the end of follow-up. Median disease-free survival for the patients at stages I–III was 63 months, and the overall survival for all patients was 50 months.Conclusion
The results of our study indicate that the survival of the patients with stomach cancer increases with chemotherapy. Radiotherapy was used for our patients with gastric cancer in specific cases.19.
M. Costa Rivas G. Huidobro Vence J. L. Fírvida Pérez B. Campos Balea J. García Gonzalez M. Lázaro Quintela M. Caeiro Muñoz B. Taboada Valladares J. E. Castro Gómez S. Vázquez Estevez F. J. Afonso Afonso C. Azpitarte Raposeiras M. Amenedo Gancedo J. Casal Rubio 《Clinical & translational oncology》2018,20(11):1467-1473
Purpose
The aim of this phase II study was to evaluate the activity and safety of the combination of cisplatin and vinorelbine with thoracic radiotherapy in unresectable locally advanced stage III non-small cell lung cancer (NSCLC). The primary endpoint was the objective response rate (ORR). Secondary objectives included toxicity profile, progression-free survival (PFS), and overall survival (OS).Materials and methods
A total of 48 NSCLC patients were enrolled (median age 60 years, 52% stage IIIA and 48% stage IIIB, 52% adenocarcinoma). Patients received three cycles of chemotherapy every 21 days [intravenous cisplatin 80 mg/m2 and intravenous vinorelbine 25 mg/m2 on day 1 and oral vinorelbine on day 8 (60 mg/m2)] concurrent with radiotherapy (66 Gy, administered at 1.8 Gy per day, five consecutive days per week).Results
ORR was 79.2% (72.9% showing partial response and 6.3% showing complete response). With a median follow-up of 20.7 months, median PFS was 12 months and median OS was 36 months. Grade 3/4 toxicities were: neutropenia (14.5%), anaemia (6.2%), vomiting (2%), and oesophagitis (4.2%). No toxic deaths were reported.Conclusion
This combined regimen shows efficacy and a manageable safety profile. PFS and OS outcomes are encouraging and warrant further research.20.
Yusuke Sasaki Satoru Iwasa Shunsuke Okazaki Masahiro Goto Yasushi Kojima Atsushi Naganuma Kengo Nagashima Yushi Nagai Hidekazu Hirano Yoshitaka Honma Atsuo Takashima Ken Kato Tetsuya Hamaguchi 《Gastric cancer》2018,21(3):439-445