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1.
Naminatsu Takahara Hiroyuki Isayama Yousuke Nakai Takashi Sasaki Hironori Ishigami Hiroharu Yamashita Hironori Yamaguchi Tsuyoshi Hamada Rie Uchino Suguru Mizuno Koji Miyabayashi Dai Mohri Kazumichi Kawakubo Hirofumi Kogure Natsuyo Yamamoto Naoki Sasahira Kenji Hirano Hideaki Ijichi Keisuke Tateishi Minoru Tada Joji Kitayama Toshiaki Watanabe Kazuhiko Koike 《Journal of gastrointestinal cancer》2014,45(3):307-311
Objectives
Here, we reported an interim analysis of feasibility and safety in the first 10 cases of 30 cases in a phase II trial of intravenous and intraperitoneal paclitaxel combined with S-1 for gemcitabine-refractory pancreatic cancer with malignant ascites.Methods
Paclitaxel was administered intravenously at 50 mg/m2 and intraperitoneally at 20 mg/m2 on days 1 and 8 every 3 weeks, and S-1 was administered at 80 mg/m2/day for 14 consecutive days, followed by 7-day rest.Results
Between April 2011 and February 2012, ten patients were enrolled. A partial response was achieved in two patients (20 %) and a disease control rate of 50 %. The median time to progression and overall survival were 2.1 and 3.4 months, respectively. Malignant ascites was completely resolved in two patients (20 %). Major grade 3/4 adverse events were myelosuppression including neutropenia (50 %) and catheter-related infection (10 %).Conclusions
This novel combination chemotherapy was feasible and showed promising results in pancreatic cancer patients with malignant ascites (clinical trial registration number: UMIN000005306). 相似文献2.
Kawashima H Itoh A Ohno E Nakamura M Miyahara R Ohmiya N Hara K Kanamori A Itoh T Taki T Hirai T Hashimoto S Takeda K Goto H Hirooka Y 《Cancer chemotherapy and pharmacology》2011,68(3):677-683
Purpose
S-1 is one of the second-line candidate agents for gemcitabine-refractory unresectable pancreatic cancer. Two phase II studies have been reported for second-line chemotherapy with S-1, but these studies did not investigate introduction rate and suitable dose of second-line S-1. Therefore, we conducted a prospective multicenter study in which chemo-na?ve patients were enrolled and had two levels of S-1 dose.Methods
Chemo-na?ve patients with unresectable pancreatic cancer were enrolled. This study started with 80?mg/m2/day dose of S-1 as second-line chemotherapy and tolerability was checked. When tolerability was not confirmed in initial patients, the dose of S-1 was shifted to 60?mg/m2/day. When tolerability was confirmed at 80 or 60?mg/m2/day, the study continued, and up to 20 patients were accumulated with the dose. In addition, the introduction rate of second-line S-1 was examined.Results
Six of the initial 7 patients with 80?mg/m2/day dose of S-1 completed one course of second-line chemotherapy. Twenty patients were accumulated with an 80?mg/m2/day dose of S-1. With the exception of one patient continued gemcitabine chemotherapy, two of the remaining 19 patients withdrew from this study because of toxicity during the period of gemcitabine chemotherapy. Fifteen of the remaining 17 gemcitabine-refractory patients could complete one course of S-1 as second-line chemotherapy with acceptable toxicity.Conclusions
This prospective multicenter study showed that 15 (78.9%) out of 19 chemo-na?ve unresectable pancreatic cancer patients could complete one course of 80?mg/m2/day dose of S-1 as second-line chemotherapy after first-line gemcitabine chemotherapy failure with tolerable toxicity. 相似文献3.
Kentepozidis N Soultati A Giassas S Vardakis N Kalykaki A Kotsakis A Papadimitraki E Pantazopoulos N Bozionellou V Georgoulias V 《Cancer chemotherapy and pharmacology》2012,70(1):161-168
Introduction
To evaluate the efficacy and tolerance of biweekly paclitaxel and carboplatin combination in patients with castration-resistant prostate cancer.Patients and methods
Patients were treated with paclitaxel at the dose of 135?mg/m2 followed by carboplatin AUC 3 on day 1 every 2?weeks in cycles of 28?days.Results
Thirty-eight patients with castration-resistant prostate cancer were enrolled, and all of them had received frontline chemotherapy with docetaxel and prednisone, while 24 (63.2?%) had received 2 or more prior chemotherapy regimens. In an intention-to-treatment analysis, a clinical and/or biochemical response (>50?% decline) was observed in 10 patients (26.3?%; 95?% CI, 12.3?C40.3?%), stable disease in 13 (34.2?%) and progressive disease in 15 (39.5?%). The median duration of response was 6.1?months (range, 1.0?C9.8), the median time to tumor progression (TTP) 3.6?months (95?% CI, 2.1?C5.2) and the median overall survival 9.9?months (95?% CI, 6.2?C13.6). The probability for 1-year survival was 43?%. Grade 3 and 4 neutropenia was observed in three (7.9?%) and nine (23.7?%) patients, respectively.Conclusion
The biweekly administration of paclitaxel/carboplatin regimen in patients with castration-resistant prostate cancer is an active and well-tolerated regimen which merits to be further evaluated in the context of salvage treatment. 相似文献4.
Ando T Hosokawa A Kajiura S Itaya Y Ueda A Fujinami H Nishikawa J Kobayashi T Horikawa N Tsukioka Y Yabushita K Note M Ogawa K Sugiyama T 《Gastric cancer》2012,15(4):427-432
Background
Only partial cross-resistance between docetaxel and paclitaxel has been demonstrated in breast and ovarian cancers. Whether weekly paclitaxel is effective in patients with advanced gastric cancer refractory to docetaxel-based chemotherapy remains unclear, and we aimed to clarify the efficacy and safety of weekly paclitaxel in such patients.Methods
Patients who had received docetaxel-based regimens were assigned to the prior-docetaxel group, and those who had never received docetaxel were designated as the non-docetaxel group. Paclitaxel at 80?mg/m2 was administered by intravenous infusion in all patients, and this was repeated weekly for 3?weeks out of 4.Results
Between April 2006 and June 2011, 65 patients were studied: 26 in the prior-docetaxel group and 39 patients were non-docetaxel group. The median age, gender, performance status, histological type, history of gastrectomy, and the locations and numbers of metastatic sites did not differ significantly between the two groups. In the prior-docetaxel group, the response rate (RR) was 14.2% (3/21) among patients with measurable lesions, median progression-free survival (PFS) was 79?days [95% confidence interval (CI), 47–135?days], and overall survival (OS) was 123?days (95% CI, 90–215?days) from the initiation of paclitaxel treatment. In the non-docetaxel group, the RR was 11.5% (3/26) among patients with measurable lesions, PFS was 82?days (95% CI, 52–106?days), and OS was 143?days (95% CI, 121–178?days). The efficacy of weekly paclitaxel thus appeared to be similar in the two groups.Conclusions
Weekly paclitaxel was modestly active in patients with gastric cancer refractory to docetaxel-based chemotherapy. 相似文献5.
Haruhiko Imamoto Koji Oba Junichi Sakamoto Hiroyasu Iishi Hiroyuki Narahara Takeyoshi Yumiba Takashi Morimoto Masaki Nakamura Noboru Oriuchi Chieko Kakutani Satoshi Morita Hitoshi Shiozaki 《Gastric cancer》2011,14(1):81-90
Background
Paclitaxel has shown promise against advanced gastric cancer and associated malignant ascites with non-measurable lesions. In order to evaluate the therapeutic effect of paclitaxel against malignant gastric ascites, a prospective phase II clinical trial was designed according to our previously proposed criteria represented by the clinical benefit response in gastric cancer (CBR-GC) criteria and the five-point method (5PM).Methods
Patients with advanced gastric cancer with malignant ascites were treated with 1-h intravenous (i.v.) infusions of 80?mg/m2 of paclitaxel weekly over a 3-week cycle on days 1, 8, and 15, followed by 1?week of rest. Therapeutic responses were measured according to the CBR-GC criteria and the 5PM.Results
The CBR-GC criteria showed improved ascites volume and functional status in 39.1% of patients. A positive CBR-GC response in abdominal girth was seen in 31.3% of patients, and this was significantly correlated with the 5PM-estimated change in ascites volume (p?<?0.001). The median number of treatment cycles was 3 (range 1?C12). The most common non-hematological toxicity was anorexia, in 22.2% of patients.Conclusion
Weekly i.v. paclitaxel is a safe and effective chemotherapeutic regimen based on validated CBR-CG criteria. 相似文献6.
Kenjiro Aogi Masayuki Yoshida Yoshiaki Sagara Shunji Kamigaki Minoru Okazaki Jumpei Funai Toshio Fujimoto Masakazu Toi Toshiaki Saeki Shigemitsu Takashima 《Cancer chemotherapy and pharmacology》2011,67(5):1007-1015
Purpose
Gemcitabine (GEM)?Cpaclitaxel combination therapy has been confirmed as a standard therapy for metastatic/recurrent breast cancer (MBC) in Western countries. This study was conducted to assess the efficacy and safety of GEM?Cpaclitaxel combination therapy in Japanese MBC patients.Methods
Patients were administered paclitaxel 175?mg/m2 on day 1, and GEM 1,000 or 1,250?mg/m2 on days 1 and 8 of 21-day cycle. The primary endpoint of this study was overall response rate; secondary endpoints were duration of response, time to progression, survival time and rate.Results
Paclitaxel 175?mg/m2 plus GEM 1,250?mg/m2 was determined as the recommended dose. A total of 56 patients received 506 cycles of treatment (median: 7.5 cycles) with a relative dose intensity of 79.6% for GEM and 85.8% for paclitaxel. The response rate was 44.6% (25/56 patients), median time to progression 8.6?months and median survival time 27.1?months. In triple-negative patients, the response rate was 35.7% (5/14 patients), and the median time to progression was 6.0?months. The most frequent grade????3 toxicities were neutropenia (82.1%), leukopenia (62.5%) and ALT increase (14.3%).Conclusions
This study confirmed the efficacy and safety of GEM?Cpaclitaxel combination therapy in Japanese MBC patients. 相似文献7.
Kentaro Sudo Taketo Yamaguchi Kazuyoshi Nakamura Tadamichi Denda Taro Hara Takeshi Ishihara Osamu Yokosuka 《Cancer chemotherapy and pharmacology》2011,67(2):249-254
Purpose
The primary objective of this study was to assess the efficacy and safety of S-1 in patients with gemcitabine-resistant advanced pancreatic cancer.Methods
Patients with histologically or cytologically proven, advanced pancreatic cancer who had received first-line chemotherapy with gemcitabine were eligible for this study. S-1 was administered orally at a dose of 40?mg/m2 twice daily for 28?days, followed by 14?days?? rest. Treatment was repeated every 6?weeks until disease progression.Results
Twenty-one patients were enrolled in this study. Grade 3 and 4 toxicities included anorexia in 14% of the patients, abdominal pain in 4.8% and infection without neutropenia in 4.8%. S-1 was discontinued in two patients because of toxicity. Of the 21 eligible patients, 2 (9.5%) achieved a partial response and 9 (43%) had stable disease. A marked decrease (??50%) in tumor marker (CA19-9) was observed in 5 (28%) of the 18 evaluable patients. The median progression-free survival and the median survival time from the first day of S-1 therapy were 4.1?months (95% CI, 1.3?C6.9?months) and 6.3?months (95% CI, 3.6?C8.9?months), respectively.Conclusions
Second-line chemotherapy with S-1 was tolerated with acceptable toxicity and resulted in a relatively high disease control rate in patients with gemcitabine-resistant advanced pancreatic cancer. As an oral agent, S-1 may be a feasible treatment option for this patient population. 相似文献8.
Noriyuki Masuda Shunichi Negoro Frederick Hausheer Kazuhiko Nakagawa Kaoru Matsui Shinzoh Kudoh Koji Takeda Nobuyuki Yamamoto Naruo Yoshimura Yasuo Ohashi Masahiro Fukuoka 《Cancer chemotherapy and pharmacology》2011,67(3):533-542
Purpose
We conducted a phase I trial of BNP7787 (disodium 2,2??-dithio-bis-ethane sulfonate, Tavocept?), a novel chemoprotective and antitumor enhancing agent administered in combination with paclitaxel and cisplatin. The primary aim was to determine a safe and potentially efficacious BNP7787 dose for preventing and mitigating paclitaxel- and cisplatin-induced toxicities and to evaluate for preliminary evidence of efficacy of treatment.Patients and methods
Twenty-two patients with stage IIIB/IV non-small cell lung cancer (NSCLC) received BNP7787 alone 1 week before co-administration of BNP7787 with paclitaxel followed by cisplatin. Twenty-one patients were treated with BNP7787 in escalating doses of 4.1?C41.0?g/m2 concurrently with paclitaxel 175?mg/m2 and cisplatin 75?mg/m2 every 3?weeks.Results
The appropriate dose was determined to be 18.4?g/m2 of BNP7787 although no dose-limiting toxicity was observed up to 41.0?g/m2. Mild intravenous site discomfort, thirst, and nausea were the most common toxicities. One patient developed grade 2 skin rash, which was severe enough to preclude further study treatment. The AUC0-inf of the metabolite mesna was approximately 6.3% of the AUC0-inf of BNP7787. Co-administration of paclitaxel and cisplatin did not appear to influence the pharmacokinetics of BNP7787 and mesna. The overall response rate was encouraging; 43% including 11 patients with prior chemotherapy.Conclusions
The recommended dose for phase II/III studies is 18.4?mg/m2 of BNP7787 in combination with paclitaxel and cisplatin. Further studies are warranted to assess whether BNP7787 prevents and mitigates common and serious paclitaxel- and cisplatin-related side effects and enhances the efficacy of paclitaxel and cisplatin in advanced NSCLC patients. 相似文献9.
Andrew H. Ko Thach-Giao Truong Emily Kantoff Kimberly A. Jones Elizabeth Dito Anna Ong Margaret A. Tempero 《Cancer chemotherapy and pharmacology》2012,70(6):875-881
Background
Substantial antitumor activity has previously been demonstrated with the addition of nab-paclitaxel (Abraxane [Celgene, Summit, NJ]), an albumin-bound formulation of paclitaxel, to gemcitabine in patients with advanced pancreatic cancer. Given preclinical evidence of synergy when a fluoropyrimidine is added to gemcitabine plus a taxane in a sequence-specific schedule, we conducted a phase I study to evaluate the combination of nab-paclitaxel, gemcitabine, and capecitabine administered biweekly in patients with metastatic pancreatic adenocarcinoma.Materials and methods
Patients with previously untreated metastatic pancreatic cancer and an ECOG performance status of 0?C1 were eligible to participate. Study design utilized a 3?+?3 dose-escalation schema, with expanded cohort at maximum-tolerated dose (MTD). Treatment was administered in 14-day cycles, with capecitabine given on days 1?C7 and both gemcitabine (at fixed-dose rate infusion) and nab-paclitaxel on day 4 of each cycle. Dose-limiting toxicity (DLT) definitions included grade 3?C4 hematologic toxicities and grade 2?C4 hand?Cfoot syndrome, neuropathy, or diarrhea.Results
Fifteen patients were enrolled across two dose levels. Final MTD was established at nab-paclitaxel 100?mg/m2, gemcitabine 750?mg/m2, and capecitabine 750?mg/m2 twice daily. Patients received a median of four treatment cycles (range 1?C16). The most frequent adverse events (any grade) for the entire study cohort included fatigue, rash/hand?Cfoot syndrome, nausea/vomiting, diarrhea, neuropathy, and elevated liver function tests. Ten patients (66.7?%) experienced at least one grade 3?C4 adverse event. Grade 3?C4 hematologic toxicities were uncommon. Two of 14 evaluable patients (14.3?%) exhibited a partial response, and 6 of 12 patients (50?%) with elevated CA19?C9 at baseline had a ??50?% biomarker decline.Conclusion
While well tolerated overall, this regimen demonstrated only modest antitumor activity in patients with metastatic pancreatic cancer. Recognizing the limits of cross-study comparisons and small sample size, these results do not match those reported at MTD in the phase I/II trial of gemcitabine/nab-paclitaxel. The lower doses used in the current study suggest that dose intensity may be a critical aspect to optimize multidrug regimens. 相似文献10.
Bulitta JB Zhao P Arnold RD Kessler DR Daifuku R Pratt J Luciano G Hanauske AR Gelderblom H Awada A Jusko WJ 《Cancer chemotherapy and pharmacology》2009,63(6):1035-1048
Purpose
Our objective was to build a mechanism-based pharmacodynamic model for the time course of neutropenia in cancer patients following paclitaxel treatment with a tocopherol-based Cremophor-free formulation (Tocosol Paclitaxel®) and Cremophor® EL-formulated paclitaxel (Taxol®).Methods
A randomized two-way crossover trial was performed with 35 adult patients who received 175 mg/m2 paclitaxel as either 15 min (Tocosol Paclitaxel) or 3 h (Taxol) intravenous infusions. Paclitaxel concentrations were measured by LC–MS/MS. NONMEM VI was used for population pharmacodynamics.Results
The cytotoxic effect on neutrophils was described by four mechanism-based models predicated on known properties of paclitaxel that used unbound concentrations in the central, deep peripheral or an intracellular compartment as forcing functions. Tocosol Paclitaxel was estimated to release 9.8% of the dose directly into the deep peripheral compartment (DPC). All models provided reasonable fitting of neutropenic effects. The model with the best predictive performance assumed that this dose fraction was released into 22.5% of the DPC which included the site of toxicity. The second-order cytotoxic rate constant was 0.00211 mL/ng per hour (variability: 52% CV). The relative exposure at the site of toxicity was 2.21 ± 0.41 times (average ± SD) larger for Tocosol Paclitaxel compared to Taxol. Lifespan was 11.0 days for progenitor cells, 1.95 days for maturating cells, and 4.38 days for neutrophils. Total drug exposure in blood explained half of the variance in nadir to baseline neutrophil count ratio.Conclusions
The relative exposure of unbound paclitaxel at the site of toxicity was twice as large for Tocosol Paclitaxel compared to Taxol. The proposed mechanism-based models explained the extent and time course of neutropenia jointly for both formulations. 相似文献11.
Bulitta JB Zhao P Arnold RD Kessler DR Daifuku R Pratt J Luciano G Hanauske AR Gelderblom H Awada A Jusko WJ 《Cancer chemotherapy and pharmacology》2009,63(6):1049-1063
Purpose
Our objectives were (1) to compare the disposition and in vivo release of paclitaxel between a tocopherol-based Cremophor-free formulation (Tocosol Paclitaxel®) and Cremophor® EL-formulated paclitaxel (Taxol®) in human subjects, and (2) to develop a mechanistic model for unbound and total paclitaxel pharmacokinetics.Methods
A total of 35 patients (average ± SD age: 59 ±13 years) with advanced non-hematological malignancies were studied in a randomized two-way crossover trial. Patients received 175 mg/m2 paclitaxel as 15 min (Tocosol Paclitaxel) or 3 h (Taxol) intravenous infusion in each study period. Paclitaxel concentrations were determined by LC–MS/MS in plasma ultrafiltrate and whole blood. NONMEM VI was used for population pharmacokinetics.Results
A linear disposition model with three compartments for unbound paclitaxel and a one-compartment model for Cremophor were applied. Total clearance of unbound paclitaxel was 845 L/h (variability: 25% CV). The prolonged release with Tocosol Paclitaxel was explained by the limited solubility of unbound paclitaxel of 405 ng/mL (estimated) in plasma. The 15 min Tocosol Paclitaxel infusion yielded a mean time to 90% cumulative input of 1.14 ± 0.16 h. Tocosol Paclitaxel was estimated to release 9.8% of the dose directly into the deep peripheral compartment. The model accounted for the presence of drug-containing nanodroplets in blood.Conclusions
Population pharmacokinetic analysis indicated linear disposition and a potentially higher bioavailability of unbound paclitaxel following Tocosol Paclitaxel administration due to direct release at the target site. The prolonged release of Tocosol Paclitaxel supports 15 min paclitaxel infusions. This mechanistic model may be important for development of prolonged release formulations that distribute in and from the systemic circulation. 相似文献12.
SF Jones JR Infante DS Thompson A Mohyuddin JC Bendell DA Yardley HA Burris 《Cancer chemotherapy and pharmacology》2012,70(3):471-475
Purpose
To determine the maximum tolerated doses and dose-limiting toxicities of oral panobinostat in combination with paclitaxel and carboplatin when administered to patients with advanced solid tumors.Patients and methods
Patients initially received panobinostat twice weekly. Following amendment #1, patients received panobinostat three times weekly. Paclitaxel and carboplatin were administered intravenously on day 1 of each 21-day treatment cycle. Dose escalation continued until the maximum tolerated dose was determined. A total of 10 patients were treated at the recommended phase II dose to further assess safety.Results
Twenty-one patients were enrolled across four different dose levels. The dose-limiting toxicity of the combination regimen was myelosuppression (neutropenia and thrombocytopenia), which often warranted panobinostat dose omissions or reductions. Nearly two-thirds of the patients experienced grade 4 neutropenia or grade 3 or 4 thrombocytopenia. Non-hematologic toxicities consisted primarily of diarrhea, fatigue, and vomiting, which were mild to moderate in intensity. No QTc prolongation was reported. Three partial responses were confirmed in patients with carcinoma of unknown primary (two patients) and non-small-cell lung cancer (one patient). Eleven additional patients reported stable disease as their best response to treatment.Conclusions
The recommended phase II dose is panobinostat 10?mg orally three times weekly in combination with paclitaxel 175?mg/m2 and carboplatin AUC 5 administered intravenously on day 1 of every 21-day cycle. 相似文献13.
Yanzhi Bi Dongxiang Zeng Yizhong Dong Guifeng Sheng Honglei Song Yang Ling 《中德临床肿瘤学杂志》2013,12(6):273-278
Objective:There remains no standard first-line chemotherapeutic regimen for advanced gastric cancer (AGC).The aim of this study was to evaluate the efficacy and safety of combination regimen with weekly paclitaxel and S-1 as a first-line chemotherapy for AGC. Methods:Forty-six patients with AGC were included in this study. Paclitaxel was administered weekly at a dose of 60 mg/m2 on days 1, 8 and 15, S-1 was administered orally twice daily at 80 mg/m2/day for 2 weeks. The regimen was repeated every four weeks. Results:The results showed that the overall response rate was 45.7%, with 3 patients achieved complete response and 18 patients had a partial response, the disease control rate was 76.1%. The median progress free survival was 7.2 months 95% confidence interval (CI):6.3-8.1 months and the median overall survival was 11.6 months (95% CI:10.6-12.6 months) after treatment with paclitaxel and S-1. Neutropenia occurred in 25 patients (54.3%) and grade 3/4 neutropenia was observed in 8 patients (17.4%), gastrointestinal reactions were the most common non-hematologic toxicities, while severe gastrointestinal toxicities were uncommon. Conclusion:The regimen of weekly paclitaxel and S-1 demonstrated activity and acceptable toxicity for AGC as a first-line chemotherapy. 相似文献
14.
Andrew H. Ko Alan P. Venook Emily K. Bergsland R. Kate Kelley W. Michael Korn Elizabeth Dito Brian Schillinger Janet Scott Jimmy Hwang Margaret A. Tempero 《Cancer chemotherapy and pharmacology》2010,66(6):1051-1057
Purpose
No standard of care exists for patients with metastatic pancreatic cancer following progression on first-line chemotherapy. Based on potential for additive or synergistic activity by concurrent inhibition of VEGF and EGFR, we conducted a phase II study evaluating the combination of bevacizumab plus erlotinib in this patient population.Methods
Patients with metastatic pancreatic adenocarcinoma, ECOG performance status 0–1, and previous exposure to 1–3 systemic therapies (at least one gemcitabine-based) were eligible. Treatment consisted of bevacizumab 15 mg/kg every 21 days plus erlotinib 150 mg daily.Results
Thirty-six patients were enrolled, including eight who had previously received VEGF-targeted therapy and nine prior erlotinib. Median number of treatment cycles was 2 (range, 1–7). Common toxicities included rash (72%), diarrhea (25%), venous thromboembolic events (15%), and hypertension (11%). One patient demonstrated partial response and seven others stable disease for >2 cycles. CA19-9 decline ≥25% was observed in 4/26 patients with baseline levels >2x ULN. Estimated median time to progression was 40 days (95% CI, 35–41 days) and median survival 102 days (95% CI, 74–117 days), with a 6-month survival rate of 22%. Baseline concentration of circulating endothelial cells (CD45?/CD34+/CD31+) was inversely associated with overall survival.Conclusions
The combination of bevacizumab and erlotinib is safe but relatively ineffective in patients with gemcitabine-refractory metastatic pancreatic cancer. Future studies should focus on refining subsets of patients in this challenging population likely to benefit from treatment beyond first-line. 相似文献15.
Na-Young Lee Kyung-Bok Lee Young-Sook Kang 《Cancer chemotherapy and pharmacology》2014,73(5):1041-1045
Purpose
Today, cancer incidence during pregnancy is increasing as women delay childbearing until later in life. Therefore, chemotherapy is regularly administered in pregnant women with cancer. In the present study, we evaluated the change in the pharmacokinetics and the fetus distribution of paclitaxel during pregnancy using pregnant rats.Methods
Pharmacokinetic parameters, placenta, and brain transport of [3H]paclitaxel were investigated in nonpregnant or pregnant rats using single intravenous injection technique.Results
The plasma pharmacokinetics of paclitaxel in pregnant rats was markedly different compared with nonpregnant rats. The V dss and CL of paclitaxel in pregnant rats were increased, and AUC was decreased compared with nonpregnant rats. The fetus uptake of paclitaxel is markedly lower than the placenta uptake. Paclitaxel is a substrate of P-glycoprotein (P-gp), so P-gp would affect the transport of paclitaxel to the fetus. The brain uptake of [3H]paclitaxtel was about twofold lower than that of nonpregnant rats.Conclusions
Current findings are important when considering cancer treatment with paclitaxel during pregnancy. 相似文献16.
Y Miyata K Nomata K Ohba T Matsuo Y Sagara H Kanetake H Sakai 《Cancer chemotherapy and pharmacology》2012,70(3):451-459
Purpose
The prognosis of patients with advanced and recurrent urothelial cancer (UC) is poor. Although cisplatin (CDDP)-containing chemotherapy is the most effective regimen in these patients, there is no other established chemotherapeutic regimen. We administered combination therapy with low-dose gemcitabine (GEM) and paclitaxel (PTX), named low-dose gemcitabine?Cpaclitaxel (LD-GP) therapy, as salvage therapy for these patients. The aim was to evaluate the anti-tumoral effects, relief of pain, and toxicity of LD-GP therapy in patients with resistance to CDDP-containing therapy.Patients and methods
Thirty-five patients with advanced UC, previously treated with CDDP-containing regimens, were treated with LD-GP therapy (GEM, 700?mg/m2?+?PTX, 70?mg/m2 on day 1 and 8, repeated every 28?days). Pain was measured on a visual analog scale before and after treatment. Pain relief and survival were compared between this and other treatment regimens.Results
None of the patients had complete response to LD-GP therapy. Partial response and stable disease were seen in 25.7 and 62.9?% of patients, respectively. Kaplan?CMeier curves showed better survival in patients with LD-GP therapy than with others (p?=?0.034). Twenty-eight patients (80.0?%) had adequate pain relief, and only two patients needed to increase their analgesics. Other regimens demonstrated pain relief in 30.4?% of patients. Common toxicities included leukopenia, with five patients requiring granular colony-stimulating factor therapy (14.3?%). The most common non-hematologic toxicity was fatigue (n?=?7, 17.1?%).Conclusions
LD-GP therapy is feasible and well tolerated as salvage therapy in patients with advanced UC with resistance to CDDP-containing therapy. 相似文献17.
Hiroyuki Yamaguchi Hiroshi Soda Yoichi Nakamura Mineyo Takasu Nanae Tomonaga Hirofumi Nakano Seiji Doi Katsumi Nakatomi Seiji Nagashima Hiroshi Takatani Minoru Fukuda Tomayoshi Hayashi Kazuhiro Tsukamoto Shigeru Kohno 《Cancer chemotherapy and pharmacology》2011,67(2):331-338
Purpose
Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that has dramatic effects in selective patients with non-small cell lung cancer (NSCLC). A simple non-invasive method for predicting the efficacy of gefitinib is preferable in clinical settings. In this study, we evaluated prospectively whether surfactant protein-A (SP-A) and -D (SP-D) may be new conventional predictors of the efficacy of gefitinib treatment.Methods
We measured serum SP-A and SP-D levels on days 0 and 29 in 40 patients with advanced NSCLC treated with 250?mg gefitinib daily. Eligibility criteria included performance status ??3, age ??80?years, and stage IIIB?CIV disease. In addition, EGFR mutations were analyzed in 24 patients.Results
Multivariate analysis showed that favorable progression-free survival (PFS) after gefitinib treatment was associated with adenocarcinoma and high serum SP-D levels before treatment. EGFR mutation analysis of 24 patients showed that 16 patients had exon 19 deletion and/or exon 21 point mutations. EGFR mutations were significantly correlated with response to gefitinib and serum SP-D levels before treatment was significantly high in patients with the EGFR mutations. Serum SP-A levels were not associated with PFS.Conclusions
The present study showed that measurement of serum SP-D levels before treatment in patients with NSCLC may be a new surrogate marker for predicting the response to gefitinib. 相似文献18.
Fernando Rivera Maica Gal��n Josep Tabernero Andres Cervantes Ma Eugenia Vega-Villegas Javier Gallego Berta Laquente Edith Rodr��guez Alfredo Carrato Pilar Escudero Bartomeu Massut�� Vicente Alonso-Ordu?a Adelaida Cardenal Alberto S��enz Jordi Giralt Ana Lucia Yuste Antonio Ant��n Enrique Aranda 《Cancer chemotherapy and pharmacology》2011,67(1):75-82
Purpose
The prognosis of patients with unresectable M0 gastric cancer remains very poor. We performed a phase II trial to explore the efficacy and toxicity of induction irinotecan-cisplatin (IC) followed by concurrent irinotecan-cisplatin and radiotherapy (IC/RT) in this setting.Methods and materials
Patients with unresectable M0 gastric (GC) or oesophageal-gastric junction (EGJC) adenocarcinomas were treated with two courses of IC (irinotecan, 65?mg/m2; cisplatin, 30?mg/m2 on days 1 and 8 every 21?days) followed by IC/RT (daily radiotherapy??45?Gy??with concurrent IC: irinotecan, 65?mg/m2, and cisplatin, 30?mg/m2, on days 1, 8, 15, and 22). Resectability was reassessed after this treatment, and surgical resection was performed if feasible. The primary endpoint was the R0 resection rate after induction treatment.Results
Seventeen patients were included in the study (EGJC: 6; GC: 11). An R0 resection was achieved in only 5 patients (29%), and according to the design of the trial (Simon??s optimal two-stage) accrual of patients was terminated after the first stage. No patient died during IC, whereas 3 patients (24%) died during IC/RT and one of 5 resected patients (20%) died during the first 30?days after resection. The median survival was 10.5?months, and the actuarial 2-year survival rate was 27%.Conclusions
Induction IC followed by IC/RT showed poor efficacy and significant toxicity in patients with unresectable GC/EGJC. 相似文献19.
Norikazu Masuda Takahiro Nakayama Jun Yamamura Shunji Kamigaki Tetsuya Taguchi Mai Hatta Junichi Sakamoto 《Cancer chemotherapy and pharmacology》2010,66(1):89-94
Purpose
Although anthracycline is a key agent in breast cancer treatment, its use is associated with the risk of cardiotoxicity. Recently, the value of combination therapy with docetaxel and cyclophosphamide was reported. Because the characteristics of paclitaxel differ on weekly versus tri-weekly administration, such as in the induction of apoptosis and anti-angiogenic activity, establishment of a treatment regimen with a combination of paclitaxel and cyclophosphamide (PC) is warranted. We initiated a phase I study to determine the maximum tolerated dose (MTD) and recommended dose (RD) of combination therapy with PC for advanced or recurrent breast cancer.Patients and methods
Eligible patients had advanced or recurrent breast cancer. Paclitaxel was given intravenously on days 1, 8, and 15 of every 3-week course, and cyclophosphamide on day 1, over a total of four courses. Paclitaxel was given at 80 mg/m2 for level 1 and 100 mg/m2 for level 2, and cyclophosphamide at 600 mg/m2 in both cases. Onset of dose-limiting toxicity was evaluated during the first course, and tolerability throughout the four courses.Results
Four patients were enrolled in each of levels 1 and 2 from October 2006 to November 2007. The main toxicities were grade 3 neutropenia in four patients (50%) and sensory neuropathy in one (12.5%). An MTD was not attained, as neither a hematologic toxicity of grade 4 nor a non-hematologic toxicity of grade 3 or higher was observed during the first course at level 1 or 2. Response rate amongst assessable patients (one in level 1, two in level 2) was 66.7%.Conclusions
Safety was well tolerated throughout the four courses at level 2, and this dosage level was therefore regarded as the RD. 相似文献20.
Prediction of paclitaxel sensitivity by CDK1 and CDK2 activity in human breast cancer cells
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Satoshi Nakayama Yasuhiro Torikoshi Takeshi Takahashi Tomokazu Yoshida Tamotsu Sudo Tomoko Matsushima Yuko Kawasaki Aya Katayama Keigo Gohda Gabriel N Hortobagyi Shinzaburo Noguchi Toshiyuki Sakai Hideki Ishihara Naoto T Ueno 《Breast cancer research : BCR》2009,11(1):R12-10