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1.
Francesca De Felice Karen Llange Filippo Rubini Nadia Bulzonetti Rossella Caiazzo Daniela Musio Vincenzo Tombolini 《Clinical colorectal cancer》2018,17(1):e77-e81
Introduction
We report the treatment compliance, toxicity rates, and long-term clinical outcomes of elderly patients who received intensified neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC).Patients and Methods
We identified a retrospective cohort of patients aged ≥ 70 years with LARC who received intensified neoadjuvant CRT, followed by surgery and adjuvant chemotherapy, from 2007 to 2014. Intensified neoadjuvant CRT consisted of radiotherapy (total dose, 50.4/54 Gy) with concomitant oxaliplatin (50 mg/m2/wk) and 5-fluorouracil (200 mg/m2 in 5 daily continuous infusion).Results
A total of 26 patients were included. All patients completed the programmed CRT. Severe acute toxicity was recorded in 19.2% of cases. Conservative surgery was performed in 16 patients, and a pathologic complete response was achieved in 19.2%. Overall, 26.9% of the patients died. The 5-year overall survival and disease-free survival rates were 70.6% and 65.5%, respectively.Conclusions
Intensified neoadjuvant CRT is an efficacious and safe treatment option for LARC in elderly patients. 相似文献2.
Tetsuya Kusumoto Eiji Sunami Mitsuyoshi Ota Kazuhiro Yoshida Yoshiyuki Sakamoto Naohiro Tomita Atsuyuki Maeda Izumi Mochizuki Michio Okabe Katsuyuki Kunieda Junichiro Yamauchi Michio Itabashi Kenjiro Kotake Keiichi Takahashi Hideo Baba Narikazu Boku Keisuke Aiba Megumi Ishiguro Kenichi Sugihara 《Clinical colorectal cancer》2018,17(2):e153-e161
Background
This trial was designed to verify the superiority of 6 months of postoperative adjuvant chemotherapy with SOX (S-1 with oxaliplatin) with UFT (tegafur and uracil) with LV (leucovorin) in terms of disease-free survival in patients with high-risk stage III colon cancer. We report the results of a planned safety analysis.Patients and Methods
Patients who underwent curative resection for high-risk stage III colon cancer (any T, N2, or positive nodes around the origin of the feeding arteries) were randomly assigned to receive either UFT/LV (300-600 mg/d UFT with 75 mg/d LV on days 1-28, every 35 days, for 5 cycles) or SOX (100 mg/m2 of oxaliplatin on day 1 with 80-120 mg/d S-1 on days 1-14, every 21 days, for 8 cycles). Treatment status and safety were evaluated.Results
A total of 966 patients were enrolled, and 932 patients were included in safety analyses. The planned 6-month protocol treatment was received by 76.9% of the patients in the UFT/LV group and 65.8% of those in the SOX group. The overall incidence of any Grade adverse events (AEs) were 91.3% in the UFT/LV group and 98.7% in the SOX group, and those of Grade ≥ 3 AEs were 16.1% and 36.1%, respectively. As for Grade ≥ 3 AEs, leukopenia, neutropenia, thrombocytopenia, and sensory neuropathy were more common in the SOX group. The incidence of Grade ≥ 3 sensory peripheral neuropathy was 4.6% in the SOX group.Conclusion
The completion rate of adjuvant SOX and its incidence of AEs were acceptable in patients with colon cancer. 相似文献3.
Shinichi Toyooka Norihito Okumura Hiroshige Nakamura Masao Nakata Motohiro Yamashita Hirohito Tada Shinsuke Kajiwara Naoki Watanabe Morihito Okada Junichi Sakamoto Motoi Aoe Junichi Soh Shinichiro Miyoshi Katsuyuki Hotta Keitaro Matsuo Hiroshi Date 《Journal of thoracic oncology》2018,13(5):699-706
Introduction
We conducted a randomized controlled study to compare the survival benefit of paclitaxel plus carboplatin and oral uracil-tegafur (UFT) as adjuvant chemotherapy in resected NSCLC.Methods
In an open-label multicenter trial, patients with pathological stage IB to IIIA NSCLC were randomized into a group receiving paclitaxel (175 mg/m2) plus carboplatin (area under the curve 5) every 3 weeks for four cycles (arm A) or a group receiving orally administered UFT (250 mg/m2) daily for 2 years (arm B). The primary and secondary end points were overall survival and relapse-free survival and toxicity, respectively.Results
Between November 2004 and November 2010, 402 patients from 40 institutions were included (201 in each arm). The median follow-up period was 6.5 years. The 5-year overall survival rate was 70% (95% confidential interval [CI]: 63–76] in arm A versus 73% (95% CI: 66–78) in arm B (hazard ratio = 0.92, 95% CI: 0.55–1.41, p = 0.69). There was no significant difference in the 5-year relapse-free survival rate between arms A and B (56% versus 57% [hazard ratio = 0.92, 95% CI: 0.63–1.34, p = 0.50]). Toxicities were well tolerated and there was no treatment-related death. Toxicities of any grade or grade 4 were significantly more frequent in the paclitaxel plus carboplatin group (95.7% and 22.1%, respectively) than in the UFT group (76.5% and 1.0%, respectively [p < 0.0001 in both]).Conclusions
As adjuvant chemotherapy, paclitaxel plus carboplatin was no better than UFT in terms of survival among patients with stage IB to IIIA NSCLC tumors who underwent complete resection (UMIN000000810). 相似文献4.
Bryan M. Burt William G. Richards Hyun-Sung Lee Sylvia Bartel Marcelo C. Dasilva Ritu R. Gill Michael T. Jaklitsch Bruce E. Johnson Scott J. Swanson Raphael Bueno David J. Sugarbaker 《Journal of thoracic oncology》2018,13(9):1400-1409
Introduction
The primary objective of this single-institution phase I clinical trial was to establish the maximum tolerated dose of gemcitabine added to cisplatin and delivered as heated intraoperative chemotherapy after resection of malignant pleural mesothelioma.Methods
The extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) treatment arms were based on investigators’ assessment of patient fitness and potential for macroscopic complete resection. Previously established intracavitary dosing of cisplatin (range 175–225 mg/m2) with systemic cytoprotection was used in combination with escalating doses of gemcitabine, following a 3-plus-3 design from 100 mg/m2 in 100-mg increments.Results
From 2007 to 2011, 141 patients were enrolled and 104 completed treatment. The median age of those completing treatment was 65 years (range 43–85 years), and 22 (21%) were female. In the EPP arm (n = 59), 31 patients (53%) had the epithelioid histologic type and the median radiographic tumor volume was 236 cm3 (range 16–4285 cm3). In the P/D arm (n = 41), 29 patients (71%) had the epithelioid histologic type and the median tumor volume was 79 cm3 (range 6–1107 cm3). The operative mortality rate was 2%, and 35 and 22 serious adverse events were encountered among 27 patients (46%) and 16 patients (39%) in the EPP and P/D arms, respectively. Dose-limiting toxicity (grade 3 leukopenia) was observed in two patients who were receiving 1100 mg/m2 of gemcitabine, thus establishing the maximum tolerated dose at 1000 mg/m2, in combination with 175 mg/m2 of cisplatin. The median overall and recurrence-free survival times in treated patients were 20.3 and 10.7 months, respectively.Conclusions
Combination cisplatin and gemcitabine heated intraoperative chemotherapy can be administered safely and feasibly in the context of complete surgical resection of malignant pleural mesothelioma by EPP or P/D. 相似文献5.
Shun Lu Zhiwei Chen Chengping Hu Jian Zhang Yuan Chen Yong Song Qiong Zhao Yun Fan Gang Wu Zhiyong Ma Jian Fang Qitao Yu Zhe Liu 《Journal of thoracic oncology》2018,13(11):1743-1749
Introduction
This study aimed to compare the efficacy of first-line nedaplatin (80 mg/m2) plus docetaxel (75 mg/m2) (ND) versus cisplatin (75 mg/m2) plus docetaxel (75 mg/m2) (CD) in patients with advanced squamous cell lung carcinoma.Methods
This open-label randomized controlled phase III trial was performed at 12 hospitals in China. Patients with squamous cell lung carcinoma were randomized to four cycles of ND or CD. The primary endpoint was progression-free survival (PFS). Secondary endpoints included time to progression, best overall response, and adverse events.Results
In the intent-to-treat analysis set (ND: n = 141; CD: n = 139), median PFS was 4.63 months (95% confidence interval: 4.43–5.10) for the ND and 4.23 months (95% confidence interval: 3.37–4.53) for CD groups (p = 0.056). No significant difference in time to progression was observed between the two groups. Best overall responses and disease control rate were better with ND 51.5%, than with CD 38.1% (p = 0.033 and p = 0.0004, respectively). Grade III or IV adverse events and grade 3-4 nausea and fatigue were more frequent in the CD group compared with the ND group (all p < 0.05).Conclusions
There is no improvement in PFS with the nedaplatin and docetaxel combination in the intent-to-treat analysis. More hematologic toxicities were observed in the ND group (compared with CD), whereas more nonhematologic toxicities were observed in the CD group. ND could be a new treatment option for advanced or relapsed squamous cell lung cancer (NCT02088515 at ClinicalTrials.gov). 相似文献6.
Bianca van Veggel Adrianus J. de Langen Sayed M.S. Hashemi Kim Monkhorst Daniëlle A.M. Heideman Erik Thunnissen Egbert F. Smit 《Journal of thoracic oncology》2018,13(8):1222-1226
Introduction
EGFR exon 20 insertions comprise 4% to 9% of EGFR mutated NSCLC. Despite being an oncogenic driver, they are associated with primary resistance to EGFR tyrosine kinase inhibitors (TKIs). We hypothesized that dual EGFR blockade with afatinib, an irreversible EGFR TKI, and cetuximab, a monoclonal antibody against EGFR, could induce tumor responses.Methods
Four patients with EGFR exon 20 insertion–positive NSCLC were treated with afatinib 40 mg once daily and cetuximab 250 mg/m2 to 500 mg/m2 every 2 weeks.Results
All patients had stage IV adenocarcinoma of the lung harboring an EGFR exon 20 insertion mutation. Previous lines of treatment consisted of platinum doublet chemotherapy (n = 4) and EGFR TKI (n = 2). Three of four patients showed a partial response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Median progression-free survival was 5.4 months (95% confidence interval: 0.0 – 14.2 months; range 2.7 months – 17.6 months). Toxicity was manageable with appropriate skin management and dose reduction being required in two patients.Conclusions
Dual EGFR blockade with afatinib and cetuximab may induce tumor responses in patients with EGFR exon 20 insertion–positive NSCLC. 相似文献7.
Amy E. Chang Qian V. Wu Isaac C. Jenkins Jennifer M. Specht Vijayakrishna K. Gadi Julie R. Gralow Lupe G. Salazar Brenda F. Kurland Hannah M. Linden 《Clinical breast cancer》2018,18(1):e143-e149
Introduction
Doxorubicin in combination with cyclophosphamide is active in breast cancer; however, its use in metastatic cancer is limited owing to cardiotoxicity. Pegylated liposomal doxorubicin (PLD) was formulated to decrease the toxicity of conventional doxorubicin. We evaluated the safety and efficacy of PLD with metronomic oral cyclophosphamide.Patients and Methods
We conducted a single-arm open-label phase I/II study of PLD and oral cyclophosphamide in patients with metastatic breast cancer. In phase I, 3 escalating doses of PLD were planned (30, 35, and 40 mg/m2) with cyclophosphamide (60 mg/m2 orally daily) to determine the maximum tolerated dose (MTD). In phase II, the MTD of PLD in combination of oral cyclophosphamide was used to assess the primary endpoint of overall clinical response rate and secondary endpoints of progression-free survival, overall survival, and adverse events.Results
Thirty patients were enrolled in the study (n = 6 in phase I and n = 24 in phase II). The MTD of PLD from phase I was 30 mg/m2. The median progression-free and overall survival for the entire cohort were 6.4 months (95% confidence interval, 3.9 months to N/A) and 18.7 months (95% confidence interval, 15.1-31.5 months), respectively. A total of 21 (75%) patients had clinical benefit, including 6 (21%) patients with partial response and 15 (54%) patients with stable disease. The majority of toxicities were uncomplicated myelosuppression, and no infection or febrile neutropenia were noted in any patient.Conclusion
PLD in combination with daily oral cyclophosphamide is an active and tolerable regimen in metastatic breast cancer. 相似文献8.
Toyoaki Hida Reiko Kaji Miyako Satouchi Norihiko Ikeda Atsushi Horiike Hiroshi Nokihara Takashi Seto Tomohisa Kawakami Shintaro Nakagawa Toshio Kubo 《Clinical lung cancer》2018,19(4):e405-e415
Introduction
Atezolizumab, an anti–programmed death-ligand 1 (PD-L1) agent, is effective and well tolerated in patients with pretreated advanced non–small-cell lung cancer (NSCLC). We assessed its efficacy and safety in Japanese patients through subgroup analyses of the phase 3 OAK study (NCT02008227).Patients and Methods
Key eligibility criteria of this randomized, controlled, open-label, international study include locally advanced/metastatic NSCLC, ≥ 1 prior platinum-based chemotherapy, age ≥ 18 years, measurable disease (Response Evaluation Criteria in Solid Tumors v1.1), and Eastern Cooperative Oncology Group performance status 0 or 1. Atezolizumab 1200 mg or docetaxel 75 mg/m2 was provided intravenously every 3 weeks. Co-primary end points were overall survival (OS) in the intention-to-treat (ITT) population and those with ≥ 1% PD-L1 expression on tumor cells (TC) or tumor-infiltrating immune cells (IC; TC1/2/3 or IC1/2/3).Results
Sixty-four ITT patients were Japanese; 19 had TC1/2/3 or IC1/2/3 status. In Japanese ITT patients, median OS in the atezolizumab arm (n = 36) was longer than the docetaxel arm (n = 28; 21.3 months [95% confidence interval (CI), 11.0-not estimable (NE)] versus 17.0 months [95% CI, 12.5-NE], respectively; hazard ratio 0.80 [95% CI, 0.41-1.57]). In the TC1/2/3 or IC1/2/3 population, median OS was 21.3 months (95% CI, 15.0-NE) and NE in the atezolizumab (n = 11) and docetaxel (n = 8) groups, respectively (hazard ratio, 0.81 [95% CI, 0.22-3.05]). Atezolizumab was generally well tolerated, with no treatment-related deaths.Conclusion
Atezolizumab was effective and well tolerated in pretreated Japanese patients with NSCLC. Results are consistent with the primary analysis of OAK. 相似文献9.
Yan Xu Shuhui Deng Xuehan Mao Gang An Zengjun Li Yafei Wang Mariateresa Fulciniti Matthew Ho Jianhong Lin Weiwei Sui Wei Liu Dehui Zou Shuhua Yi Wenyang Huang Hong Liu Rui Lv Jian Li Tingyu Wang Lugui Qiu 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(6):422-430
Background
Peripheral neuropathy (PN) is an important toxicity that limits the use of bortezomib (Btz). Attempts to reduce PN have included its subcutaneous (SC) administration.Patients and Methods
We retrospectively analyzed 307 patients with newly diagnosed multiple myeloma from a single Chinese center, receiving Btz-based regimens administered either via SC injection (SC group, n = 167) or intravenous (IV) infusion (IV group, n = 140). The efficacy and safety of Btz administration via SC and IV were then compared.Results
Most baseline characteristics were similar between these 2 groups. A lower frequency of adverse events, especially grade ≥ 3 PN (P = .002), was observed in the SC group compared with the IV group. The estimated median Btz dosage when PN developed was higher (20.8 mg/m2 vs. 15.6 mg/m2), and fewer patients reduced or discontinued Btz owing to adverse events in the SC group compared with the IV group. The overall response rate (≥ partial response [PR]) was comparable (94.8% vs. 96.2%). However, patients in the IV group required fewer cycles to achieve PR, whereas a larger proportion of patients in the IV group achieved ≥ very good PR. After a median follow-up of 23 months (range, 1-84 months), no significant difference in median progression-free survival (not arrived vs. 33.0 ± 2.735 months) and overall survival (not arrived vs. 56.0 months) was noted.Conclusion
SC Btz is associated with better tolerance; however, IV administration achieves a faster and deeper response in Chinese patients with newly-diagnosed multiple myeloma. 相似文献10.
Jean Maroun Horia Marginean Derek Jonker Christine Cripps Rakesh Goel Timothy Asmis Rachel Goodwin Gabriela Chiritescu 《Clinical colorectal cancer》2018,17(2):e257-e268
Background
The objective of the present phase I study was to define the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of irinotecan, capecitabine, and oxaliplatin given in combination (IXO regimen) to patients with previously untreated, unresectable advanced or metastatic colorectal cancer (CRC).Patients and Methods
Patients received oxaliplatin followed by irinotecan as intravenous infusions on day 1, with oral capecitabine taken twice daily (BID) on days 2 to 15 of a 3-week cycle. The dose ranges were explored as follows: oxaliplatin, 75 to 120 mg/m2; irinotecan, 160 to 230 mg/m2; capecitabine, 750 to 1000 mg/m2 BID. Dose escalation was performed individually for each drug at each dose level according to the type and severity of toxicity encountered in the previous cohort.Results
A total of 39 patients were enrolled at 7 dose levels and the MTD. The recommended doses for phase II evaluation were oxaliplatin 100 mg/m2, irinotecan 160 mg/m2, and capecitabine 950 mg/m2 BID. Diarrhea and febrile neutropenia were DLTs. Of the 39 enrolled patients, 26 (67%) had confirmed objective responses. The median progression-free survival was 11 months, and the median overall survival was 25 months. The survival rate at 5 years was 23%.Conclusion
The IXO regimen has a manageable toxicity profile with promising antitumor activity as first-line treatment of advanced and metastatic CRC. 相似文献11.
Emmanouil Saloustros Michail Nikolaou Konstantinos Kalbakis Aris Polyzos Charalampos Christofillakis Nikolaos Kentepozidis Nikolaos Pistamaltzian Charalampos Kourousis Lampros Vamvakas Vasilios Georgoulias Dimitris Mavroudis 《Clinical breast cancer》2018,18(1):88-94
Background
Triple-negative breast cancer (TNBC) lacks a standard targeted therapeutic strategy and is treated with conventional cytotoxic agents. Because of the sensitivity of TNBC to platinum compounds and the synergistic effect of bevacizumab with paclitaxel we investigated the efficacy and toxicity of weekly paclitaxel and carboplatin in combination with bevacizumab as first-line treatment in metastatic TNBC.Patients and Methods
This phase II study followed the Simon’s 2-stage optimal design. Paclitaxel (90 mg/m2) and carboplatin (2 area under the curve) were administered on days 1, 8, and 15 every 4 weeks, preceded by bevacizumab 10 mg/kg on days 1 and 15. The primary end point was the objective response rate (ORR). The null hypothesis that the ORR is ≤ 40% could be rejected if the number of objective responses was ≥ 23 among 46 evaluable patients.Results
A total of 46 patients were enrolled. Seven (15.2%) complete and 23 (50%) partial responses were observed for an ORR of 65.2% (95% confidence interval, 52.9%-80.4%). The median progression-free survival was 10.3 months, the median overall survival 25.7 months, and the median duration of response 18.2 months. Neutropenia Grade III and IV was experienced by 13 (28.3%) and 6 (13.04%) patients, respectively. One patient developed an uneventful Grade IV thrombocytopenia. There was 1 toxic death due to febrile neutropenia. Other Grade III toxicities included anemia (n = 2), neurotoxicity (n = 2), thrombocytopenia (n = 1), and diarrhea (n = 1). No serious bevacizumab-related toxicities were observed.Conclusion
The study achieved its primary end point by showing clinical activity for weekly paclitaxel with carboplatin and bevacizumab combination. This regimen merits further evaluation in this setting. 相似文献12.
Nelleke P.M. Brouwer Rutger C.H. Stijns Valery E.P.P. Lemmens Iris D. Nagtegaal Regina G.H. Beets-Tan Jurgen J. Fütterer Pieter J. Tanis Rob H.A. Verhoeven Johannes H.W. de Wilt 《European journal of surgical oncology》2018,44(8):1241-1246
Background
This study aims to provide insight in the quality of current daily practice in clinical lymph node staging in colorectal cancer (CRC) in the Netherlands.Methods
Data of the nationwide population-based Netherlands Cancer Registry between 2003 and 2014 were used to analyze lymph node staging for cM0 CRC patients. Accuracy of clinical lymph node staging was calculated for the period 2011–2014. Analyses were performed for patients without preoperative treatment or treated with short-course radiotherapy (SCRT) followed by resection.Results
100,211 patients were included for analysis. The proportion clinically positive lymph nodes increased significantly between 2003 and 2014 (6%–22% for colon cancer; 7%–53% for rectal cancer). The proportion histological positive lymph nodes remained stable (±35% colon, ±33% rectum). Data from 2011 to 2014 yielded a sensitivity, specificity, positive and negative predictive value of 41%, 84%, 59% and 71% for colon cancer, respectively (n = 21,629). This was 38%, 87%, 56%, 76% for rectal cancer without SCRT, (n = 2178) and 56%, 67%, 47% and 75% for rectal cancer with SCRT (n = 3401), respectively.Conclusion
Accuracy of clinical lymph node staging in colorectal cancer patients is about as accurate as flipping a coin. This may lead to overtreatment of rectal cancer patients. Acceptable specificity and NPV limit the risk of undertreatment. 相似文献13.
Karen A. Cadoo Peter A. Kaufman Andrew D. Seidman Cassandra Chang Dongyuan Xing Tiffany A. Traina 《Clinical breast cancer》2018,18(6):433-440.e1
Background
Eribulin has significantly improved overall survival for patients with metastatic breast cancer who received ≥ 2 prior chemotherapy regimens for advanced disease. This trial assessed eribulin as adjuvant therapy for patients with early-stage breast cancer.Patients and Methods
Patients with human epidermal growth factor receptor 2–negative, stage I to III breast cancer received doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 provided intravenously on day 1 of each 14-day cycle for 4 cycles, with pegfilgrastim on day 2, followed by 4 cycles of eribulin mesylate 1.4 mg/m2 provided intravenously on days 1 and 8 every 21 days. There were 2 cohorts, as follows: cohort 1: no prophylactic growth factor with eribulin (allowed at physician’s discretion only); cohort 2: prophylactic filgrastim with eribulin. The primary end point was feasibility, defined as the percentage of patients who completed the eribulin portion of the regimen without a dose omission, delay, or reduction due to an eribulin-related adverse event. Relative dose intensity of eribulin and toxicities are summarized by cohort. Exploratory end points included 3-year disease-free survival and overall survival.Results
Eighty-one patients (cohort 1, n = 55; cohort 2, n = 26) entered the treatment phase; 88% completed treatment. Feasibility was 72.9 % (90% confidence interval, 60.4, 83.2) in cohort 1 and 60.0% (90% confidence interval, 41.7, 76.4) in cohort 2. The most frequent eribulin-related adverse events (all grades) were fatigue (75.9%), peripheral neuropathy (54.4%), nausea (39.2%), neutropenia (35.4% [31.5% of patients in cohort 1; 44.0% in cohort 2]), and arthralgia (26.6%).Conclusion
The primary end point of > 80% feasibility was not met. No unexpected adverse events were observed, and 62% of patients received full dosing with no dose delay or reduction. Further investigation of this regimen with alternative dosing schedules or use of growth factors could be considered. 相似文献14.
Cheol-Kyu Park In-Jae Oh Kyu-Sik Kim Yoo-Duk Choi Tae-Won Jang Youn-Seup Kim Kwan-Ho Lee Kyeong-Cheol Shin Chi Young Jung Sei-Hoon Yang Jeong-Seon Ryu Seung-Hun Jang Seung-Soo Yoo Suk-Joong Yong Kye Young Lee Kwang-Ho In Min-Ki Lee Young-Chul Kim 《Clinical lung cancer》2017,18(4):e289-e296
Introduction
To date, no prospective phase III trials have directly compared the efficacy of pemetrexed plus cisplatin (Pem-Cis) with docetaxel plus cisplatin (Doc-Cis) in patients with nonsquamous non–small-cell lung cancer.Materials and Methods
A total of 148 chemotherapy-naive patients lacking driver mutations were randomized into 21-day regimens of cisplatin 70 mg/m2 with either docetaxel 60 mg/m2 (n = 71) or pemetrexed 500 mg/m2 (n = 77) for ≤ 4 cycles. The primary objective was to assess the noninferiority of progression-free survival (PFS) for patients receiving the Doc-Cis regimen. The secondary endpoints were the response rates, overall survival, and toxicity profiles.Results
Partial remission was observed in 24 (31.2%) and 24 (33.8%) patients in the Pem-Cis and Doc-Cis groups, respectively. The median PFS was 4.7 months (95% confidence interval [CI], 4.4-5.0) in the Pem-Cis arm and 4.4 months (95% CI, 3.7-5.1) in the Doc-Cis arm (P > .05). The median overall survival was longer in the Doc-Cis arm (13.3 months; 95% CI, 8.1-18.5) than in the Pem-Cis arm (11.7 months; 95% CI, 8.6-14.8; P > .05). Between the 2 arms, no significant difference was found in the subsequent treatments after failure of first-line treatment. The rate of grade 3 or 4 neutropenia and febrile neutropenia was greater in the Doc-Cis arm than in the Pem-Cis arm.Conclusion
In nonsquamous non–small-cell lung cancer patients lacking driver mutations, the PFS and response rates were similar between the 2 arms, and toxicity was tolerable, although adverse events and more severe toxicities were observed more frequently in the Doc-Cis arm. 相似文献15.
Bruno Mendonça Protásio Adriana Matutino Liana Valente Lage Iuri Santana Ricardo Ramos Jorge Sabbaga Fernanda Capareli Daniel Saragiotto Rachel Riechelmann Paulo M. Hoff 《Clinical colorectal cancer》2017,16(1):65-72
Background
The efficacy and safety of the combination of a fluoropyrimidine with oxaliplatin for patients with stage III colorectal cancer (CRC) have been evaluated in selected patients who took part in clinical trials. We evaluated the outcomes of FLOX (bolus fluorouracil [5-FU] combined with oxaliplatin) in patients with resected stage III CRC treated in the community in a large cancer center.Patients and Methods
We performed a retrospective unicenter cohort study of all consecutive stage III CRC patients who received adjuvant chemotherapy with an mFLOX (modified FLOX) regimen. The schedule consisted of 5-FU bolus 500 mg/m2 and bolus of leucovorin 20 mg/m2 per week for 6 consecutive weeks and oxaliplatin 85 mg/m2 in a 2-hour infusion at weeks 1, 3, and 5, every 8 weeks. Logistic regression multivariate analyses were used to evaluate prognostic factors for relapse at 2 years, and to investigate potential predictors of Grade ≥3 toxicity.Results
A total of 267 consecutive patients were eligible and included. The median age was 59 years and pathological stage was mostly IIIB (68.2%). With a median follow-up of 24 months, n = 67 patients (25.1%) relapsed, representing a 74.9% rate of disease-free survival at 2 years. In multivariable analyses, urgent surgery (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.02-3.48; P = .042), angiolymphatic invasion (OR, 1.92; 95% CI, 1.05-3.52; P = .034), and any interruption or dose reduction of chemotherapy (OR, 2.37; 95% CI, 1.31-4.27; P = .004) were predictors of recurrence or death at 2 years. Nine patients (3.4%) died from any cause within 60 days of starting mFLOX. Grade ≥3 toxicity occurred in 98 (36.7%) patients, with diarrhea (n = 43; 16.1%) and neutropenia (n = 38; 15.3%) being the most frequent ones. Peripheral neurotoxicity Grade ≥3 occurred in 5 patients (1.8%). Age 70 years or older (OR, 5.85; 95% CI, 2.5-13.66; P ≤ .001) was independently associated with a higher risk of a Grade ≥3 adverse events.Conclusion
Results suggest that the effectiveness of combining oxaliplatin with bolus 5-FU in patients in the community is reasonably similar to that obtained in clinical trials. However, community patients presented a higher risk of death, especially for those who were older than 70 years. Adjuvant oxaliplatin should be used carefully and probably restricted to fit patients younger than 70 years in this setting. 相似文献16.
Suresh S. Ramalingam Maurice Pérol Martin Reck Ruben Dario Kowalyszyn Oliver Gautschi Martin Kimmich Eun Kyung Cho Grzegorz Czyzewicz Alexandru Grigorescu Nina Karaseva Shaker Dakhil Pablo Lee Annamaria Zimmerman Andreas Sashegyi Ekaterine Alexandris Gebra Cuyun Carter Katherine B. Winfree Edward B. Garon 《Clinical lung cancer》2018,19(3):270-279.e3
Introduction
Ramucirumab, a recombinant human immunoglobulin G1 monoclonal antibody receptor antagonist designed to block the ligand-binding site of vascular endothelial growth factor receptor-2 (VEGFR-2), was evaluated as second-line treatment in combination with docetaxel in patients with non–small-cell lung cancer in the REVEL trial (NCT01168973). Ramucirumab significantly improved overall survival (OS) and progression-free survival (PFS). We report age subgroup analysis results primarily on the basis of a 65-year cutoff.Patients and Methods
Patients were randomized 1:1 to ramucirumab with docetaxel or placebo with docetaxel (n = 1253). Of these, 798 were younger than 65 years (ramucirumab, n = 391; control, n = 407) and 455 were 65 years or older (ramucirumab, n = 237; control, n = 218). Treatment comprised 21-day cycles of 75 mg/m2 docetaxel with 10 mg/kg ramucirumab or placebo. Prespecified age subgroup analyses were performed, including OS, PFS, and objective response rate. Quintiles age analysis was conducted to establish a relationship between efficacy and age. The Lung Cancer Symptom Scale (LCSS) measured quality of life outcomes. Safety was assessed according to adverse events (AEs).Results
Patients younger than 65 years showed favorable OS outcomes with ramucirumab treatment (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.62-0.87; P < .001) and PFS (HR, 0.68; 95% CI, 0.59-0.79; P < .001). In patients 65 years or older, benefits of ramucirumab were not as evident; after model adjustment for prognostic factors, OS and PFS HRs were 0.96 (95% CI, 0.77-1.21; P = .04) and 0.87 (95% CI, 0.71-1.05; P = .03), respectively. Age analysis according to quintiles showed HRs favoring ramucirumab for all age groupings. LCSS scores and AEs did not considerably differ between age groups.Conclusion
In this subgroup analysis, true treatment effect differences on the basis of age have not been established, and treatment should not be deterred solely because of age. 相似文献17.
Mark A. Socinski Frederic J. Kaye David R. Spigel Fred J. Kudrik Santiago Ponce Peter M. Ellis Margarita Majem Paul Lorigan Leena Gandhi Martin E. Gutierrez Dale Nepert Jesus Corral Luis Paz Ares 《Clinical lung cancer》2017,18(1):68-76.e2
Introduction
This trial assessed the safety and efficacy of LM in combination with carboplatin/etoposide therapy compared to carboplatin/etoposide treatment alone in patients with previously untreated extensive-disease small-cell lung cancer (ED-SCLC).Patients and Methods
A run-in phase 1 stage was used to determine the recommended phase 2 dose and characterize the dose-limiting toxicities of LM in combination with carboplatin/etoposide followed by LM alone in patients with CD56-positive solid tumors. In phase 2, chemotherapy-naive ED-SCLC patients were randomized 2:1 to carboplatin AUC (area under the plasma concentration vs. time curve) of 5 day 1 + etoposide 100 mg/m2 days 1 to 3 plus LM (arm 1) or alone (arm 2).Results
In the phase 1 study (n = 33), a dose of LM at 112 mg/m2 with carboplatin/etoposide was identified as the recommended phase 2 dose. However, because of an increased incidence of peripheral neuropathy events during early phase 2, this dose was reduced to 90 mg/m2. In phase 2, a total of 94 and 47 evaluable patients were assigned to arms 1 and 2, respectively. No difference in median progression-free survival was observed between arms 1 and 2 (6.2 vs. 6.7 months). The most common treatment-emergent adverse event leading to discontinuation was peripheral neuropathy (29%). A total of 21 patients had a treatment-emergent adverse event leading to death (18 in arm 1 and 3 in arm 2); for 10 individuals, this was an infection (pneumonia or sepsis) deemed to be related to the study drug.Conclusion
The combination of LM plus carboplatin/etoposide did not improve efficacy over standard carboplatin/etoposide doublet therapy in ED-SCLC patients and showed increased toxicity, including a higher incidence of serious infections with fatal outcomes. 相似文献18.
Malin Enblad Wilhelm Graf Helgi Birgisson 《European journal of surgical oncology》2018,44(7):997-1005
Background
Early diagnosis to target minimal volume disease has received increased attention in the management of appendiceal and colorectal peritoneal metastases (PM). This study aimed to identify risk factors for appendiceal, colon and rectal PM.Methods
Data were retrieved from the Swedish Colorectal Cancer Registry for all patients undergoing bowel resection of appendiceal and colorectal tumours, in Sweden, 2007–2015. Risk factors for synchronous and metachronous PM were analysed with multivariate logistic and Cox proportional hazard regression models.Results
Synchronous PM was most common in appendiceal cancer (23.5%), followed by colon (3.1%) and rectal (0.6%) cancer. The 5-year cumulative incidence was 9.0% for appendiceal, 2.5% for right colon, 1.8% for left colon and 1.2% for rectal cancer. In appendiceal cancer (n = 327), T4, N2, mucinous tumour, and non-radical surgery were associated with PM. In colon cancer (n = 24,399), synchronous PM were primarily associated with T4 (OR 18.37, 95% CI 8.12–41.53), T3 and N2 but also with N1, right-sided tumour, mucinous tumour, vascular and perineural invasion, female gender, age <60 and emergency surgery. These factors were also associated with metachronous PM. In rectal cancer (n = 10,394), T4 (OR 19.12, 95% CI 5.52–66.24), proximal tumour and mucinous tumour were associated with synchronous PM and T4 and mucinous tumour with metachronous PM.Conclusions
This study shows that appendiceal cancer, right-sided colon cancer, advanced tumour and node stages and mucinous histopathology are the main high-risk features for PM and should increase the awareness of current or future PM. 相似文献19.
S. Gollins S. Massalha A. Mullard R.M. Williams A. Lloyd J. Morris A. Garcia-Alonso 《Clinical oncology (Royal College of Radiologists (Great Britain))》2018,30(7):409-417
Aims
This open-label prospective phase I/II dose-escalation study determined the maximum tolerated dose (MTD) and then evaluated response, safety and feasibility of a novel combination of docetaxel, cisplatinum and capecitabine (DCC) in chemotherapy-naive patients with advanced oesophago-gastric carcinoma.Materials and methods
Patients with adenocarcinoma or squamous cell carcinoma of the oesophagus or stomach, of good performance status, deemed too advanced for curative treatment, were given systematically increasing doses of 3 weekly DCC to ascertain the MTD. Phase II administered up to six cycles of DCC at the MTD, assessing response and toxicity.Results
Between November 2007 and November 2012, 15 patients were recruited into phase I and 41 into phase II. The MDT was a 21 day cycle of docetaxel 60 mg/m2 IV day 1, cisplatinum 60 mg/m2 IV day 1 and oral capecitabine 1000 mg/m2 daily in two divided doses for days 1–21. The most common phase II grade 3–4 toxicities were neutropenia 88% (10% febrile neutropenia), fatigue 15%, sensory neuropathy 10% and non-neutropenic infection 10%. The overall response rate was 51%, median progression-free survival was 7.4 months (confidence interval 6.7–9.4) and median overall survival was 10.9 months (confidence interval 7.7–13.7).Conclusion
DCC was tolerable and feasible with promising efficacy, and may be suitable for future investigation in both first-line metastatic and neoadjuvant settings. 相似文献20.
Sewha Kim Byung-In Moon Woosung Lim Sanghui Park Min Sun Cho Sun Hee Sung 《Clinical breast cancer》2018,18(5):e1123-e1132