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1.
G. Bisagni A. Musolino M. Panebianco A. De Matteis F. Nuzzo A. Ardizzoni S. Gori T. Gamucci R. Passalacqua R. Gnoni G. Moretti C. Boni 《Cancer chemotherapy and pharmacology》2013,71(4):1051-1057
Background
Therapeutic approach for patients with metastatic breast cancer (MBC) is still controversial. This study was conducted to assess the efficacy and safety of bevacizumab in combination with docetaxel plus capecitabine as first-line treatment for MBC. The feasibility of bevacizumab maintenance therapy in this setting was also evaluated.Patients and methods
In this single-arm, multicenter phase II study, patients received bevacizumab 15 mg/kg and docetaxel 60 mg/m2 on day 1, plus capecitabine 900 mg/m2 twice daily on days 1–14 every 21 days. Treatment was administered for up to 6 cycles, then bevacizumab continued until progressive disease. The primary end point was progression-free survival (PFS); secondary end points were tumor response rate, overall survival, and toxicity.Results
Seventy-nine eligible patients were treated with bevacizumab in combination with docetaxel plus capecitabine. The overall response rate was 61 %, with a complete response rate of 8 % and a median duration of response of 10 months. At a median follow-up of 28 months, the median PFS was 11 months. Fifty-two (65 %) patients received bevacizumab maintenance therapy for a median duration of 7 months (range 1 to 33+). Neutropenia was the most common grade 3–4 toxicity (28.1 % of patients), and two fatal adverse events occurred (septic shock and gastrointestinal perforation).Conclusions
Bevacizumab in combination with docetaxel and capecitabine demonstrates significant activity and quite acceptable toxicity profile as first-line treatment of MBC. Subsequent maintenance therapy with bevacizumab is feasible for a long period of stable disease. Results deserve confirmation. 相似文献2.
Yago Nieto José Manuel Aramendía Jaime Espinós Susana De la Cruz Oscar Fernández-Hidalgo Marta Santisteban Leyre Arbea Javier Aristu Rafael Martínez-Monge Marta Moreno Luis Pina Josu Sola Gerardo Zornoza Fernando Martínez Regueira 《Cancer chemotherapy and pharmacology》2010,65(3):457-465
Purpose
Capecitabine is effective against metastatic breast cancer (MBC). We hypothesized that sequential treatment with dose-dense epirubicin/cyclophosphamide (EC) and docetaxel/capecitabine would be active and tolerable in the adjuvant/neoadjuvant setting.Methods
In this prospective phase II clinical trial patients with HER2-negative and node-positive or locally advanced tumors were eligible to receive four cycles of EC (100/600 mg/m2) every 2 weeks with G-CSF on days 3–10, followed by four cycles of docetaxel/capecitabine (75/1,000 mg/m2 b.i.d., days 1–14) every 3 weeks.Results
Fifty-five patients were enrolled with median age of 49, and 80% had hormone receptor-positive disease. The median tumor size was 2.5 cm, with a median of two axillary nodes involved. Seventy-five percent of the first 20 patients had grade 2/3 hand-foot syndrome (HFS). Dose reduction of capecitabine to 800 mg/m2 reduced the grade 2/3 HFS incidence to 31% in the remaining patients. No grade 4/5 toxicities were observed. All 20 patients treated preoperatively responded, with 5 (25%) pathologic complete responses and 3 additional pT0N1 tumors. At a median follow-up of 48 (range 28–60) months, the event-free and overall survival rates are 91 and 98%, respectively.Conclusions
Sequential treatment with dose-dense EC followed by docetaxel/capecitabine, using a lower capecitabine dose than that approved for MBC, has an acceptable toxicity profile and encouraging activity when used as neoadjuvant or adjuvant treatment of breast cancer. 相似文献3.
Ourania Katopodis Aris Polyzos Nikolaos Kentepozidis Stylianos Giassas Maria Rovithi Vasiliki Bozionelou Kostas Kalbakis Lambros Vamvakas Dimitris Mavroudis Vassilis Georgoulias 《Cancer chemotherapy and pharmacology》2011,67(2):361-368
Purpose
To investigate the efficacy and toxicity of the docetaxel and capecitabine combination in patients with previously treated, unresectable adenocarcinoma of the pancreas.Patients and Methods
Patients with pancreatic adenocarcinoma, pre-treated with gemcitabine-based chemotherapy, were treated with capecitabine (800?mg/m2 orally, twice a day for 14?days) and docetaxel (75?mg/m2 i.v, on day1), every 3?weeks. The primary end-point was overall response rate (RR).Results
Thirty-one patients were enrolled in the study; 93.6% of them had a performance status (PS) of 0?C1 and 96.8% had stage IV disease. Patients received a median of 4 cycles/patient, and the main reason for treatment discontinuation was disease progression. Partial response was observed in three (9.7%) patients, stable disease in seven (22.6%) (disease control rate: 32.3%, 95% CI: 15.80?C48.71%) and disease progression in 21 (67.6%). The median progression-free survival (PFS) was 2.4?months (95% CI: 1.6?C3.13) and the median overall survival (OS) was 6.3?months (95% CI: 3.38?C9.23); the estimated 1-year survival rate was 14.7%. Grade III/IV neutropenia occurred in 10 (32.2%) patients and febrile neutropenia in one patient. Other severe non-hematologic toxicities were mild and manageable. After 2 chemotherapy cycles, pain control occurred in 20% of patients and stabilization of body weight in 40%.Conclusion
The combination of docetaxel/capecitabine may confer good disease control associated with improvement of quality of life as second-line chemotherapy in patients with metastatic pancreatic cancer. 相似文献4.
Luigi Di Lauro Patrizia Vici Franca Belli Silverio Tomao Silvia Ileana Fattoruso Maria Grazia Arena Laura Pizzuti Diana Giannarelli Giancarlo Paoletti Maddalena Barba Domenico Sergi Marcello Maugeri-Saccà 《Gastric cancer》2014,17(4):718-724
Background
The incorporation of docetaxel into the cisplatin and fluorouracil backbone has been demonstrated to be an active combination in metastatic gastric cancer. Nevertheless, this regimen is burdened by nonnegligible toxicity. We hypothesized that replacing cisplatin and fluorouracil with oxaliplatin and capecitabine should be an active and safe option for metastatic gastric cancer patients.Methods
In this phase II study, we tested the activity of docetaxel in combination with oxaliplatin and capecitabine (DOC) as a first-line treatment. DOC was administered as follows: docetaxel (60 mg/m2) and oxaliplatin (100 mg/m2) on day 1, and capecitabine (500 mg/m2) was administered orally twice daily given continuously, with cycles repeated every 3 weeks. The primary endpoint was the overall response rate.Results
Forty-eight patients entered the study. All patients had metastatic disease (stage IV). None of the patients had previously received chemotherapy for advanced disease. Performance status was 0, 1, and 2 in 25, 58, and 17 % of patients, respectively; 13 patients (27 %) had adenocarcinoma of the gastroesophageal junction, and 29 patients (60.5 %) had two or more metastatic sites. The overall response rate was 52.1 %. Progression-free survival and overall survival were 6.9 and 12.6 months, respectively. The treatment was well tolerated with no treatment-related deaths. The most common grade 3–4 toxicity was neutropenia (41 %).Conclusions
DOC is an effective and tolerated first-line treatment, and the lower dose of docetaxel and oxaliplatin used in this study compared with other similar regimens does not seem to hamper the antitumor activity. 相似文献5.
Sun Jin Sym Min-Hee Ryu Hye Jin Kang Sung Sook Lee Heung-Moon Chang Jae Lyun Lee Tae Won Kim Jeong Hwan Yook Sung Tae Oh Byung Sik Kim Yoon-Koo Kang 《Cancer chemotherapy and pharmacology》2010,66(2):373-380
Purpose
Adding docetaxel to cisplatin and 5-fluorouracil (5-FU) (DCF) significantly improved clinical efficacy in advanced gastric cancer (AGC). To further improve the efficacy and tolerability, we substituted oxaliplatin for cisplatin and capecitabine for 5-FU in the DCF regimen and performed a phase I study to determine the recommended dose (RD) and dose-limiting toxicity (DLT) of docetaxel, capecitabine and oxaliplatin (DXO) combination in patients with AGC.Materials and methods
Previously untreated patients with histologically proven metastatic AGC and ECOG performance status 0–2 were enrolled. Docetaxel and oxaliplatin were administered i.v. on day 1. Capecitabine was administered orally bid on days 1–14. Each cycle was repeated every 3 weeks. DLTs were evaluated during the first two cycles of treatment.Results
Twenty-one patients were enrolled: 15 patients in dose-escalation phase and 6 patients in the extension at the RD. Median age was 50 years (range 21–65 years). At dose level 3 (60 mg/m2 docetaxel, 1,000 mg/m2 capecitabine, 100 mg/m2 oxaliplatin), 1 diarrhea (DLT) was found among 6 patients while at dose level 4 (60 mg/m2 docetaxel, 800 mg/m2 capecitabine, 130 mg/m2 oxaliplatin), 2 DLTs (febrile neutropenia and diarrhea) were observed among 3 patients. Therefore, the dose level 3 was determined as RD. DLTs include grade 3 diarrhea and febrile neutropenia. Cumulative (all cycles) grade 3/4 toxicity included neutropenia (75%), leucopenia (50%), febrile neutropenia (25%), diarrhea (17%), and neuropathy (17%). Of 14 patients with measurable lesions, 11 achieved partial response and 3 showed stable disease.Conclusion
The RD of the DXO regimen in patients with AGC is capecitabine 1,000 mg/m2 twice daily on days 1–14, in combination with decetaxel 60 mg/m2 (day 1) and oxaliplatin 100 mg/m2 (day 1) repeated every 3 weeks. The DXO regimen seems to have promising activity and offers an easy alternative to DCF. The toxicities appear to be still substantial, but manageable. 相似文献6.
Kazuhiro Yanagihara Kenichi Yoshimura Miyuki Niimi Hiroyasu Yasuda Takahiko Sasaki Takafumi Nishimura Hiroshi Ishiguro Shigemi Matsumoto Toshiyuki Kitano Masashi Kanai Akiko Misawa Harue Tada Satoshi Teramukai Tadashi Mio Masanori Fukushima 《Cancer chemotherapy and pharmacology》2010,66(5):913-918
Purpose
The purpose of the present phase II study was to evaluate both the efficacy and toxicity of the combination of S-1 and docetaxel in previously treated patients with locally advanced or metastatic non-small cell lung cancer.Methods
Thirty-eight previously treated patients with non-small cell lung cancer were treated with S-1 (80 mg/m2, days 1–14, oral) and docetaxel (40 mg/m2, day 1, intravenous) every 3 weeks.Results
No complete response was observed, and seven patients had a partial response, yielding an overall response rate of 18.4% (95% CI, 7.7–34.3%). The median overall survival time and 1-year overall survival rate were 16.1 months and 60%, respectively. The median progression-free survival time was 4.4 months. Myelosuppression was the main toxicity with grade 3 or 4 neutropenia and leukopenia in 50 and 21%, respectively. There was no irreversible toxicity in this study.Conclusions
The combination of S-1 and docetaxel is well tolerable and has substantial activity for patients with locally advanced or metastatic non-small cell lung cancer. A phase III trial comparing docetaxel with or without S-1 would warrant further investigation. 相似文献7.
Ji Soo Park Hei-Cheul Jeung Sun Young Rha Joong Bae Ahn Beodeul Kang Hong Jae Chon Min Hee Hong Seungtaek Lim Woo Ick Yang Chung Mo Nam Hyun Cheol Chung 《Cancer chemotherapy and pharmacology》2014,74(4):799-808
Purpose
We conducted a phase II study evaluating safety and efficacy of combination gemcitabine and capecitabine therapy for metastatic breast cancer patients following anthracycline and taxane treatment in Korea.Methods
This was a single-arm, non-randomized phase II study. Patients received 1,000 mg/m2 gemcitabine intravenously over 30 min on days 1 and 8, and 1,250 mg/m2 capecitabine orally twice daily on days 1–14 until disease progression or intolerable toxicity occurred. This regimen was repeated every 3 weeks. The primary outcome assessed was overall response rate [ORR, complete response (CR) + partial response (PR) as the best response], and secondary outcomes were progression-free survival (PFS), overall survival (OS), disease control rate (DCR) [maintenance of CR + PR + stable disease (SD) for at least 3 months], drug toxicity, and predictive factors for response to this regimen.Results
Of 41 patients, the ORR was 39.0 % (CR 0 %; PR 39.0 %), and DCR was 78.0 % using this chemotherapy. DCR for 6 and 12 months was 68.3 and 26.8 %, respectively. Median PFS was 10.0 months [95 % confidence interval (CI) 7.8–12.1], and median OS was 25.1 months (95 % CI 18.2–32.1). Prominent toxicities were neutropenia and hand–foot syndrome. Most adverse events were well known, relatively moderate, and reversible. Taxane sensitivity [odds ratio (OR) 0.169; 95 % CI 0.034–0.826; P = 0.028] and hepatic metastasis (OR 0.097; 95 % CI 0.017–0.559; P = 0.009) were significantly predictive of response to gemcitabine and capecitabine combination.Conclusions
This study showed reproducible anticancer activity and tolerable toxicity of gemcitabine and capecitabine combination therapy in recurrent or metastatic Korean breast cancer patients previously treated with anthracycline and taxane. 相似文献8.
Hesham Tawfik Yousri Rostom Hesham Elghazaly 《Cancer chemotherapy and pharmacology》2013,71(4):913-919
Purpose
To evaluate the efficacy and safety of an all-oral vinorelbine and capecitabine combination therapy in anthracycline- ± taxane-pretreated HER2/Neu-negative metastatic breast cancer (MBC).Methods
A phase 2 trial including women >18 years with HER2/Neu-negative MBC previously exposed to anthracycline- ± taxane-based chemotherapy in the adjuvant or neoadjuvant setting. Enrolled patients received oral vinorelbine 60 mg/m2 on days 1 and 8 and oral capecitabine 1,000 mg/m2 twice daily on days 1–14 on a 3 weekly schedule. Patients with progressive disease after 3 cycles discontinued the study, while the remaining patients continued treatment for a maximum of 6 cycles.Results
From January 2007 to March 2011, 30 patients were enrolled in this study (median age 47 years). In the 28 evaluable patients, the overall response rate was 57.1 % (95 % CI 30–67 %), including 3 complete (10.7 %) and 13 partial (46.4 %) responses. Six (21.4 %) patients suffered from disease progression. With a median follow-up time of 13 months, the median time to disease progression was 8.6 months (95 % CI 6.2–10.6 months) and the median survival time was 27.2 months. Treatment-related adverse events were manageable, and no World Health Organization grade 4 toxicities were noted. Neutropenia observed in 6 (21.4 %) patients was the main grade 3 toxicity. Grade 3 nausea and vomiting were reported in 2 (7.1 %) and 3 (10.7 %) patients, respectively. Two (7.1 %) patients developed grade 3 hand and foot syndrome.Conclusion
These results show that the combination of oral vinorelbine and capecitabine is an effective and well-tolerated first-line regimen for HER2/Neu-negative MBC patients pretreated with anthracyclines ± taxanes. 相似文献9.
Kunitoshi Shigeyasu Shunsuke Kagawa Futoshi Uno Masahiko Nishizaki Hiroyuki Kishimoto Akira Gochi Toshikazu Kimura Takaomi Takahata Yasuyuki Nonaka Motoki Ninomiya Toshiyoshi Fujiwara 《Cancer chemotherapy and pharmacology》2013,71(4):937-943
Purpose
Peritoneal dissemination is the most frequent and life-threatening mode of metastasis and recurrence in patients with gastric cancer. A multicenter phase II study was designed to evaluate the efficacy and tolerability of S-1 and docetaxel combination chemotherapy regimen for the treatment of advanced or recurrent gastric cancer patients with peritoneal dissemination.Methods
Nineteen patients with histologically confirmed unresectable or recurrent gastric cancer with peritoneal dissemination were enrolled. Oral S-1 at 80 mg/m2/day was administered twice daily for 2 weeks, followed by 1 drug-free week. Docetaxel infusion at 40 mg/m2 was performed on day 1, simultaneous with S-1 administration. The primary endpoints were overall survival (OS) and time to progression (TTP). The secondary endpoints were the response rates and safety status.Results
Patients received a median of 4 cycles of the S-1 and docetaxel regimen (range 1–43). The disease control rate was 73.7 % (14/19). Median overall survival was 459 days (15.3 months), while median time to progression was 212 days (7.1 months). Neutropenia was the most common type of toxicity (n = 7, 36.8 %).Conclusions
Combination chemotherapy with S-1 and docetaxel is a tolerable and effective treatment for advanced or recurrent gastric cancer patients with peritoneal dissemination. 相似文献10.
Kimio Ushijima Toshiharu Kamura Kazuo Tamura Kazuo Kuzuya Toru Sugiyama Kiichiro Noda Kazunori Ochiai 《International journal of clinical oncology / Japan Society of Clinical Oncology》2013,18(1):126-131
Background
The aim of this phase II study was to evaluate the efficacy and toxicity of docetaxel and irinotecan combination chemotherapy in patients with ovarian cancer refractory and resistant to both platinum and taxan treatment.Patients and methods
Patients who had been treated with platinum and paclitaxel but whose ovarian cancer progressed or recurred within 6 months of treatment (n = 41) received docetaxel 60 mg/m2 (day 1) and irinotecan 60 mg/m2 (days 1, 8), repeated every 21 days [Japan Gynecologic Oncology Group (JGOG) study 3015] or every 28 days [West Japan Gynecologic Oncology Group (WJGOG) study 002] until disease progression was observed or unacceptable toxicity. Sixteen patients had platinum/paclitaxel-refractory disease, and 25 patients had platinum/paclitaxel-resistant disease.Results
Thirty-two patients were available for determination of the clinical response. The overall response rate [complete response (CR) + partial response (PR)] was 6.3%, and the disease control rate (CR + PR + stable disease) was 34.4%. Among the 23 patients with resistant tumor, the disease control rate was 47.8%. Ten patients with refractory tumor showed a 10% disease control rate. The median progression-free interval was 12.1 weeks and the median overall survival time was 45.3 weeks. The major toxic adverse effect was neutropenia (grade 4, 56.1%), but the incidence of neutropenic fever was less frequent (4.9%). Neurotoxicity and gastro-intestinal toxicity were mild.Conclusion
Among our patients, a combination of docetaxel and irinotecan was well tolerated. However, this combination may not be a beneficial option for patients with platinum-refractory and -resistant ovarian cancer in terms of response rate and survival. 相似文献11.
Kaisa Leea Sunela Sanna Koskinen Pirkko-Liisa Kellokumpu-Lehtinen 《Cancer chemotherapy and pharmacology》2010,66(1):59-67
Purpose
Combination of capecitabine and interferon has shown activity in metastatic renal cell carcinoma. Pegylated interferons might have more clinical activity and fewer side effects. This study evaluated the efficacy, tolerability, and safety of the combination of capecitabine and pegylated interferon alfa-2a.Methods
In this open label, single institution, non-randomized phase-II first-line study, 26 patients were included. Capecitabine was administered 2,000 mg/m2 daily for 14 days followed by 1 week rest. Pegylated interferon alfa-2a was given once as weekly injections with a fixed dose of 180 μg. Overall survival, progression-free survival, and response rates were evaluated; safety and tolerability were monitored.Results
Response rate was 27, with 4% complete responses. Stable disease was achieved in 42%. The treatment discontinued in 4 (15%) patients before first response evaluation because of toxicity. The median progression-free survival was 7.5 months; the median overall survival was 17 months. Grades 3–4 toxicity was seen in 46% of patients, but in 93% of cycles no serious toxicity was experienced. Dose reductions had to be done, but in 81% of cycles intensity of 70% or more was possible. Quality of life was better in cycle five than in the base line.Conclusions
The combination had moderate, but manageable toxicity. In the future studies, lower dose for capecitabine is recommended. The combination was active and the response rates seen here were in line with phase-II studies on former combinations of non-pegylated interferons. One complete remission was achieved. 相似文献12.
Masato Karayama Naoki Inui Shigeki Kuroishi Koshi Yokomura Mikio Toyoshima Toshihiro Shirai Masafumi Masuda Takashi Yamada Kazumasa Yasuda Takafumi Suda Kingo Chida 《Cancer chemotherapy and pharmacology》2013,72(2):445-452
Purpose
The optimal strategy for maintenance chemotherapy is controversial. We evaluated the efficacy and safety of continuation maintenance with pemetrexed and switch maintenance with docetaxel in advanced non-squamous non-small-cell lung cancer (NSCLC).Methods
Chemotherapy-naïve patients with non-squamous NSCLC were enrolled in this randomized phase II study. Patients who achieved disease control after four cycles of induction therapy with carboplatin (AUC 6) and pemetrexed (500 mg/m2) were randomized to maintenance therapy with pemetrexed (500 mg/m2) or docetaxel (60 mg/m2). The primary endpoint was survival without toxicity, defined as the time from the initiation of maintenance therapy to the first date of any grade 3/4 toxicity or death due to any cause.Results
A total of eighty-five patients were enrolled in the induction phase, and 26 patients were assigned to the pemetrexed maintenance therapy and 25 patients were assigned to the docetaxel maintenance therapy. Survival without toxicity was significantly longer in the pemetrexed group (median 20.8 months, 95 % confidence interval (CI) 0.7–not estimable) than in the docetaxel group (median 0.5 months, 95 % CI 0.2–2.0, hazard ratio 0.36, 95 % CI 0.17–0.74).Conclusions
Continuation maintenance with pemetrexed may be a feasible treatment option for patients with non-squamous NSCLC who have achieved disease control after induction therapy with carboplatin and pemetrexed. Switch maintenance with docetaxel may also be efficacious but frequently causes severe hematologic toxicity. 相似文献13.
Filippos Koinis Aristidis Polyzos Athina Christopoulou Zafeiris Zafeiriou Christos Emmanouilidis Elisavet Papadimitraki Antonia Kalykaki Kostas Kalbakis George Samonis Vassilis Georgoulias 《Cancer chemotherapy and pharmacology》2014,73(4):819-825
Purpose
To evaluate the safety and antitumor activity of docetaxel (DOC) and pegylated liposomal doxorubicin (PLD) combination in patients with platinum- and taxane-sensitive ovarian cancer.Patients and methods
Twenty-three patients were enrolled. DOC was administered at the dose of 40 mg/m2 intravenously (i.v.) and PLD at 20 mg/m2 i.v. on days 1 and 15 in cycles of 28 days. The study was closed prematurely due to slow accrual.Results
Seven (30.4 %) patients achieved objective response (three complete, four partial), while five (21.7 %) others experienced stable disease (overall disease control rate 52.1 %). The median progression-free survival was 4.8 months and the median overall survival 18.8 months. Grade 3–4 neutropenia occurred in two (8.7 %) and one (4.3 %) patients, respectively. Febrile neutropenia occurred in two patients. The most common non-hematological grade 3 toxicity was hand-foot syndrome (13 % of patients). There was no treatment-related death.Conclusions
The combination of pegylated liposomal doxorubicin and docetaxel is a well tolerated and a relatively active regimen in pretreated patients with platinum- and taxane-sensitive advanced ovarian cancer. 相似文献14.
Yixing Jiang Heath B. Mackley Eric T. Kimchi Junjia Zhu Niraj Gusani Jussuf Kaifi Kevin F. Staveley-O’Carroll Chandra P. Belani 《Cancer chemotherapy and pharmacology》2014,74(1):205-210
Purpose
Pancreatic cancer is one of the leading causes of cancer-related deaths worldwide. The median survival of locally advanced nonoperable disease is approximately 9 months. 5-FU-based chemoradiotherapy has been the standard treatment. However, the survival benefit of this approach is modest. To improve the efficacy of 5-FU-based chemoradiation therapy, we evaluated the safety and feasibility of the combination of capecitabine and erlotinib with radiotherapy in this group of patients.Experimental design
A traditional “3 + 3” dose escalation design was adopted in the study. A total of four dose levels were designed. For safety purpose, a minus I dose level (?I) was also planned. The ?I level consisted of capecitabine 600 mg/m2 and erlotinib 50 mg daily, and the remaining four dose levels were as follows: level I: capecitabine 600 mg/m2 bid (twice daily); level II: 700 mg/m2 bid; level III: 825 mg/m2 bid; and level IV: 925 mg/m2 bid. Erlotinib was administered at 100 mg daily at all dose levels. Erlotinib and capceitabine were given continuously Monday through Friday concurrent with radiotherapy (50.4 Gy in 28 fractions).Results
A total of 18 patients were consented. Fifteen patients were enrolled and completed therapy. No dose-limiting toxicity was observed. The most frequent side effects were lymphopenia, nausea, vomiting, diarrhea, electrolyte imbalances, and skin rashes. The majority of the toxicities were grade 1 and 2. No objective response was observed. The median progression-free survival was 0.59 years (95 % CI 0.31–1.1), and the median overall survival was 1.1 years (95 % CI 0.62–1.59).Conclusions
The combination of capecitabine and erlotinib with radiotherapy in locally advanced pancreatic cancer is well tolerated and feasible at the dose level of capecitabine 925 mg/m2 bid and erlotinib 100 mg daily. 相似文献15.
Jin Young Kim Young Rok Do Keon Uk Park Min Kyung Kim Kyung Hee Lee Sung Hwa Bae Hun Mo Ryoo Jin Ho Baek Hong Suk Song 《Cancer chemotherapy and pharmacology》2010,66(1):31-36
Objective
The objective of this study was to evaluate the efficacy and toxicity of docetaxel and cisplatin combination chemotherapy in patients with metastatic esophageal cancer.Methods
Patients with untreated metastatic squamous cell esophageal cancer, which was histologically proven with at least one measurable lesion, were eligible for the study. Docetaxel 70 mg/m2 and cisplatin 70 mg/m2 were intravenously given on day 1 of 21 days schedule.Results
From December 2004 to December 2007, total of 39 patients (M/F = 39/0) were enrolled. The median age was 65 years. Thirty-four patients were evaluable for response. There were 3 (7.7%) complete remission, 10 (25.6%) partial remission, 11 (28.2%) stable disease, and 10 (25.6%) progression disease. The objective tumor response rate was 33.3% in intention-to-treat (ITT). Median PFS was 5.0 months and median survival was 8.3 months. Median number of cycles administered was 3. The relative dose intensity of docetaxel and cisplatin was 92 and 91%, respectively. This treatment was comparatively tolerated with grade 3/4 neutropenia in 20.5%/10.3%, grade 3 infection in 2.6% of patients.Conclusion
Docetaxel plus cisplatin combination chemotherapy showed promising antitumor activity with manageable toxicities in patients with metastatic squamous esophageal cancer. 相似文献16.
Yuki Kita Yosuke Shimizu Takahiro Inoue Tomomi Kamba Koji Yoshimura Osamu Ogawa 《International journal of clinical oncology / Japan Society of Clinical Oncology》2013,18(4):718-723
Background
In clinical practice, an adapted regimen with dose reduction is applied to castration-resistant prostate cancer (CRPC) treated with docetaxel because of its toxicity. However, there are few reports on the impact of dose reduction on survival.Methods
Fifty-seven patients with CRPC treated with first-line docetaxel in a single institution from 2005 to 2008 were evaluated retrospectively.Results
The median follow-up period was 20.5 months. Twenty-eight patients (49 %) received a standard 60 mg/m2 regimen (SR), and 29 patients (51 %) received an adapted regimen (AR) with dose reduction. There was no difference in their baseline characteristics. The prostate-specific antigen response rates were not significantly different between the SR and AR groups (50 vs. 62 %, p = 0.36). Progression-free survival (PFS) and overall survival (OS) were also not significantly different between the groups (PFS 5.3 vs. 7.3 months, p = 0.39; OS 26.4 vs. 27.1 months, p = 0.53, respectively). No significant difference in the incidence of grade 3 or 4 adverse events was noted between the groups (89 vs. 83 %, p = 0.70). In multivariate analysis, hemoglobin and alkaline phosphatase were significant predictive factors for OS (hazard ratios 2.81 and 2.39, p = 0.012 and 0.024, respectively).Conclusions
A reduced-dose regimen of docetaxel has no inferior impact on OS. Further studies on the optimal dose of docetaxel for Japanese patients are required. 相似文献17.
M. Joerger A. D. R. Huitema D. Koeberle H. Rosing J. H. Beijnen F. Hitz T. Cerny J. H. M. Schellens S. Gillessen 《Cancer chemotherapy and pharmacology》2014,73(1):113-124
Purpose
We assessed the impact of hepatic dysfunction on the safety and pharmacology of gemcitabine/capecitabine in patients with advanced pancreatico-biliary cancer.Methods
We included 12 patients receiving 3 weekly gemcitabine 1,000 mg/m2 day 1, 8 and oral capecitabine 650 mg/m2 b.i.d. over 2 weeks until disease progression or intolerable toxicity. Patients were included into one normal hepatic function cohort [total bilirubin (TB) ≤15 μmol/L] and 3 cohorts with increasing TB (16–39, 40–80, >80 μmol/L). Three patients with a creatinine clearance <60 ml/min were also included. Patients were sampled for gemcitabine, difluoro-deoxy uridine, intracellular gemcitabine triphosphates, capecitabine, 5′-deoxy-5-fluorocytidine, 5′-deoxy-5-fluorouridine and 5-fluorouracil up to 4 h after initiation of chemotherapy on day 1, and up to 90 min on day 8. All compounds were analyzed using validated liquid chromatography–tandem mass spectrometry. Nonlinear mixed-effect modeling was used for population analysis.Results
Hepatic dysfunction was caused by intrahepatic cholestasis in 4 out of 8 patients (50 %) and extrahepatic cholestasis in another 4 patients (50 %). Dose-limiting toxicity was increasing hyperbilirubinemia and severe neutropenia in 2 patients each. Hepatic dysfunction was not associated with dose-limiting toxicity or severe hematological or non-hematological toxicity. However, hepatic dysfunction was associated with low clearance of both gemcitabine (p = 10?3) and capecitabine (p = 10?5), and low intracellular gemcitabine triphosphate concentrations (p = 10?3).Conclusions
Gemcitabine/capecitabine can be given at the standard dose in patients with severe hyperbilirubinemia, though the present data suggest that gemcitabine’s activity may be limited due to poor intracellular activation. In patients with severe hyperbilirubinemia, initial monotherapy with capecitabine should be considered, followed by the addition of gemcitabine with improving hyperbilirubinemia. 相似文献18.
Marisa E. Hill Xiaobai Li Sharon Kim Angela Campbell Kristy Culler Mark Bloomston Mark Zalupski Gwen Hejna Tanios Bekaii-Saab 《Cancer chemotherapy and pharmacology》2011,67(3):511-517
Background
Pancreas cancer remains a formidable challenge. We report the first prospective analysis of the 3-drug combination of gemcitabine (G), docetaxel (T) and capecitabine (X) (mGTX) with schedule modification to maximize biomodulation of X.Methods
We conducted a dose escalation study of mGTX in first-line treatment of metastatic pancreas cancer using three dose levels (DL 1-3). Patients received docetaxel on days 1 and 8, gemcitabine on days 8 and 15, and capecitabine on days 8 through 21. Gemcitabine dose was fixed at 750?mg/m2 over 75?min, capecitabine was given twice daily and escalated from 500 to 650?mg/m2 at DL2 and docetaxel increased from 30 to 36?mg/m2 at DL3.Results
Twenty-one patients (18 evaluable) were enrolled in the study. MTD was reached at DL3 and one DLT was observed at DL2 (prolonged neutropenia). The most common grade 3/4 toxicities were leukopenia (29%) and neutropenia (29%) and fatigue (25%). Tumor growth control rate was 80% (11% PR; 69% SD lasting at least 3?months). Median progression-free-survival was 5.8?months (95% CI 2.7, 10.6) and median overall survival was 7.4?months (95% CI 3.8 16.8). CA 19-9 decreased by at least 50% from baseline in half the patients.Conclusion
mGTX demonstrates acceptable tolerability with interesting activity in patients with pancreatic cancer. The recommended doses for phase II studies are docetaxel 36?mg/m2 days 1 and 8, gemcitabine 750?mg/m2 over 75?min days 8 and 15, and capecitabine 625?mg/m2 twice daily days 8 through 21. 相似文献19.
Purpose
The randomized phase III JO21095 trial compared the efficacy and safety of low-dose capecitabine plus docetaxel combination therapy (XT) versus single-agent administration of docetaxel in anthracycline-pretreated HER2-negative metastatic breast cancer.Methods
Patients were randomized to either low-dose XT (capecitabine 825 mg/m2 twice daily, days 1–14; docetaxel 60 mg/m2, day 1 every 3 weeks) or docetaxel (70 mg/m2, day 1 every 3 weeks). The primary objective was to demonstrate superior progression-free survival (PFS) with low-dose XT versus single-agent docetaxel. Overall survival (OS) and safety were secondary endpoints.Results
In total, 162 patients were treated. Median PFS was 10.5 months with low-dose XT and 9.8 months with single-agent docetaxel (hazard ratio [HR] 0.62 [95% confidence interval (CI) 0.40–0.97]; p = 0.03). The OS HR was 0.89 (95% CI 0.52–1.53; p = 0.68). Grade ≥3 treatment-related toxicities occurred in 74% of XT-treated patients and 76% of docetaxel-treated patients. The main differences in grade ≥3 treatment-related toxicities were hand-foot syndrome (7.3% of XT-treated patients vs 0% receiving docetaxel), fatigue/malaise (2.4 vs 10.0%), and peripheral edema (1.2 vs 7.5%). Dose modifications were required in 100% of low-dose XT and 49% of docetaxel patients. Toxicity-related treatment discontinuations occurred in 18 and 33%, respectively.Conclusion
The improved PFS with low-dose XT versus docetaxel alone is consistent with higher-dose XT phase III experience, but the safety profile was more favorable and manageable.20.