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1.
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2.
Tanaka Y Yoshida K Sanada Y Osada S Yamaguchi K Takahashi T 《Cancer chemotherapy and pharmacology》2010,66(6):1159-1165
Background and purpose
The optimal chemotherapeutic protocol for the treatment of esophageal cancer has not yet been established. A dose-escalation study of docetaxel combined with cisplatin and 5-fluorouracil (5-FU) was performed to determine the optimal dose in patients with advanced esophageal squamous cell carcinoma.Patients and method
We studied a total of 18 patients who had previously untreated thoracic esophageal squamous cell carcinoma with T4 tumors and/or metastasis. The patients received an infusion of docetaxel at different dose levels (levels 1, 2, 3: 30, 35, 40 mg/m2, respectively) and an infusion of cisplatin (40 mg/m2) on days 1 and 15 plus a continuous infusion of 5-FU (400 mg/m2/day) on days 1–5 and 15–19.Results
Dose-limiting toxicities (DLT) included febrile neutropenia and leukopenia. DLT occurred in 2 of 6 patients at level 1, 2 and in 3 of 6 patients at level 3. The response rate was 88.9%, including a complete response rate of 33.3%.Conclusions
To minimize toxicity and maximize dose intensity, we elected to investigate a biweekly regimen. The maximum tolerated dose was level 3, and the recommended dose was determined to be docetaxel 35 mg/m2 with cisplatin 40 mg/m2 plus 5-FU 400 mg/m2, administered biweekly. This regimen was tolerable and highly active. A phase II study has been started. 相似文献3.
Catalano V Vincenzi B Giordani P Graziano F Santini D Baldelli AM Alessandroni P Schiavon G Rossi D Casadei V D'Emidio S Luzi Fedeli S Tonini G Fiorentini G 《Gastric cancer》2012,15(4):419-426
Background
The combination of docetaxel, cisplatin, and 5-fluorouracil (5-FU) has demonstrated a survival advantage over cisplatin and 5-FU, but with substantial hematological toxicity. We aimed to evaluate the efficacy and toxicity of a sequential regimen with cisplatin, leucovorin, and 5-FU (PLF) followed by docetaxel in metastatic gastric cancer patients.Methods
Treatment consisted of 4 cycles of biweekly PLF (cisplatin 50?mg/m2 as a 30-min infusion on day 1, leucovorin 200?mg/m2 in a 2-h infusion, and 5-FU 2,800?mg/m2 in a 48-h continuous infusion starting on day 1) followed, in cases of response or stable disease, by 3 cycles of docetaxel (75?mg/m2, every 3?weeks).Results
Thirty-four patients were enrolled, with an average age of 64?years (range 34–69). The main cumulative grade 3–4 toxicities were: neutropenia (38.2%), febrile neutropenia (11.8%), and fatigue (14.7%). After the planned 7 cycles of treatment, the overall response rate was 38.2% (95% confidence interval [CI] 21.9–54.6), with 3 complete and 10 partial responses. Median progression-free survival and overall survival were 4.8 and 10.6?months, respectively.Conclusions
For patients with metastatic gastric cancer, the sequential administration of cisplatin, leucovorin, 5-FU, and docetaxel may be an effective palliative option and offers a far more favorable toxicity profile than the simultaneous use of docetaxel, cisplatin, and 5-FU. 相似文献4.
Apostolia M. Tsimberidou Stacy Moulder Siqing Fu Sijin Wen Aung Naing Agop Y. Bedikian Shawn Daring Cynthia Uehara Chaan Ng Michael Wallace Luis Camacho Razelle Kurzrock 《Cancer chemotherapy and pharmacology》2010,66(6):1087-1093
Purpose
We conducted a phase I study of hepatic arterial infusion (HAI) cisplatin and systemic chemotherapy in patients with advanced cancer and dominant liver involvement.Methods
Patients were treated with HAI cisplatin 100–125 mg/m2 (and 3,000 IU heparin) intraarterially and liposomal doxorubicin (doxil) 20–35 mg/m2 IV (day 1) every 28 days. A “3 + 3” study design was used.Results
Thirty patients were treated (median age, 56 years). Diagnoses were breast cancer (n = 11), colorectal cancer (n = 8), ocular melanoma (n = 4), and other (n = 7). The median number of prior therapies was 5. The maximum tolerated dose (MTD) was at the 100/35 mg/m2 level. Dose-limiting toxicities were Grade 4 neutropenia (2 of 4 patients), and Grade 4 thrombocytopenia (n = 1) at the cisplatin 125 mg/m2 and systemic doxil 35 mg/m2 dose level. The most common toxicities were nausea/vomiting and fatigue. Of 24 patients evaluable for response, 4 (17%) had a partial response (PR) and 7 (29%) had stable disease (SD) for ≥4 months. Of the 11 patients with breast cancer, 3 (27%) had a PR and 5 (45%) had SD for ≥4 months. Of 4 patients with ocular melanoma, 1 had a PR and 1 SD for 4 months. One patient with hepatocellular carcinoma had SD for 4 months. Of 12 evaluable patients treated at the MTD, 2 (17%) had a PR and 5 (42%) had SD.Conclusion
The MTD was HAI cisplatin 100 mg/m2 and systemic doxil 35 mg/m2. This regimen demonstrated antitumor activity, especially in breast cancer. 相似文献5.
Hara T Omura K Hirano M Asada Y Munemoto Y Sakamoto J 《Cancer chemotherapy and pharmacology》2007,59(5):631-636
Purpose
A phase I study of TCF therapy, which consists of paclitaxel (TXL: Taxol®) + cisplatin (CDDP) + 5-fluorouracil (5-FU), in advanced gastric cancer patients was performed to determine the recommended dose (RD) for a phase II study by checking the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of 5-FU above the fixed dose of TXL and CDDP.Methods
The doses of TXL and CDDP were fixed at 80 and 25 mg/m2, respectively, while that of 5-FU was increased by 100 mg/m2 in each cohort from 300 mg/m2 (level 1) to a maximum of 600 mg/m2 (level 4). One cycle consisted of administration of these agents once per week for 3 weeks, every 4 weeks.Results
A total of twelve eligible patients were included in this study. At level 1, two of three cases showed grade 3 leukopenia. At level 2, one of three cases showed grade 4 neutropenia (recovered within 3 days), and another one case showed grade 3 neutropenia. At level 3, one of three cases showed grade 3 neutropenia, and at level 4, one of three cases showed grade 4 neutropenia (recovered within 3 days), with grade 3 neutropenia in the other two cases. Even at the highest dose administered, none of the patients showed DLT. Moreover, no non-hematological toxicity judged to be DLT was observed through all levels. Six of the twelve patients had measurable disease, and the overall response rate was 83%.Conclusions
Although the MTD level was not determined, based on the observed efficacy and the results of other clinical trials, the recommended doses of TXL, CDDP, and 5-FU for the TCF regimen were set as 80, 25, and 600 mg/m2, respectively, and a phase II study to investigate the clinical effectiveness and safety of this regimen has now begun. 相似文献6.
Kyong Hwa Park Jeong Sun Kim Yong Park Hee Yeon Seo Young Je Park In Keun Choi Sang Chul Oh Jae Hong Seo Chul Yong Kim Kwang Yoon Jung Sang Won Shin Yeul Hong Kim Jun Suk Kim Nam Joon Lee 《Cancer chemotherapy and pharmacology》2010,66(4):643-651
Purpose
Concomitant approach using cisplatin and 5-fluorouracil (5-FU) has shown an excellent local control rate and significantly reduced distant metastasis in patients with locally advanced nasopharyngeal carcinoma (NPC). However, optimal schedule and dosing of chemotherapy still need to be developed to reduce distant metastasis. This retrospective study was conducted to evaluate the efficacy, toxicity, and tolerability of a concurrent chemoradiation therapy (CCRT) regimen using cisplatin and 5-FU followed by adjuvant chemotherapy (AC) in patients with locoregioanlly advanced NPC.Methods
Forty-three NPC patients who had AJCC stage T3/T4 or N2/N3 and M0 disease were evaluated. The chemotherapy during CCRT consisted of cisplatin (75 mg/m2 on day 1) plus 5-FU (750 mg/m2/day on day 1–5), delivered every 4 weeks for two cycles. Three cycles of AC were given with cisplatin (75 mg/m2), epirubicin (37.5 mg/m2) on day 1, and bleomycin (7.5 mg/m2 bolus iv. on day 1 followed by 9 mg/m2 on day 1–5 by continuous infusion) every 3 weeks.Results
The overall response rate after CCRT was 95% (22 CRs and 19 PRs in 43) and 100% (16 CRs and 8 PRs in 24) after AC. Grade 3/4 neutropenia, mucositis, and weight loss were observed during CCRT phase in 18, 44, and 26% of patients, respectively. AC caused grade 3/4 neutropenia and emesis in 12.5 and 20.8% of patients, respectively.Conclusions
CCRT regimen using cisplatin and 5-FU followed by three cycles of BEC chemotherapy was effective in locally advanced NPC patients, with acceptable and reversible acute toxicities. 相似文献7.
D. Ross Camidge Normand Blais Derek J. Jonker Denis Soulières Robert C. Doebele Ana Ruiz-Garcia Aron Thall Ke Zhang Scott A. Laurie Richard C. Chao Laura Q. Chow 《Cancer chemotherapy and pharmacology》2013,71(2):307-319
Purpose
To determine the maximum tolerated dose (MTD), safety and tolerability of sunitinib plus pemetrexed and cisplatin for advanced solid malignancies.Methods
Using a 3 + 3 dose-escalation design, patients received oral sunitinib (37.5 or 50 mg) qd on a continuous daily dosing (CDD) schedule or Schedule 2/1 (2 weeks on, 1 week off treatment) plus pemetrexed (400 or 500 mg/m2 IV) and cisplatin (75 mg/m2 IV) q3w up to 6 cycles.Results
Sunitinib 37.5 mg/pemetrexed 400 mg/m2/cisplatin 75 mg/m2 CDD (n = 5) was not tolerated. Lower doses on this schedule were not explored. The Schedule 2/1 MTD (n = 15) was sunitinib 37.5 mg/pemetrexed 500 mg/m2/cisplatin 75 mg/m2, based on one dose-limiting toxicity (myocardial infarction) out of six patients. The MTD was further studied in an expansion cohort of 10 non-small cell lung cancer (NSCLC) patients and one mesothelioma patient. There were no clinically significant drug–drug interactions. Cumulative myelosuppression was problematic: the median relative dose intensity (% actual/intended) across all cycles was 61 % for sunitinib, 78 % for pemetrexed, and 74 % for cisplatin. Four of eight NSCLC patients in the dose-escalation and expansion cohorts at the Schedule 2/1 MTD who were evaluable for efficacy had stable disease ≥8 weeks, and the one patient with mesothelioma had a partial response.Conclusions
In patients with advanced solid malignancies, sunitinib was not tolerated at 37.5 mg CDD with standard pemetrexed and cisplatin doses. Dose reductions were often needed due to cumulative myelosuppression following cycle 1. The MTD showed modest antitumor activity. 相似文献8.
Mori M Tsukuda M Matsuda H Horiuchi C Taguchi T Takahashi M Nishimura G Komatsu M Niho T Sakuma N Miyakoshi A Isono Y Iwahana S 《Cancer chemotherapy and pharmacology》2011,68(4):855-862
Purpose
The aim of this study was to evaluate the feasibility and toxicity of concurrent chemoradiotherapy (CCRT) with docetaxel, cisplatin (CDDP) and 5-fluorouracil (5-FU) (TPF regimen) or with CDDP, 5-FU, methotrexate and leucovorin (PFML regimen) in previously untreated patients with advanced oropharyngeal squamous cell carcinoma (SCC).Methods
Fifty-six eligible patients with stage III or IV oropharyngeal SCC were treated with CCRT. Forty-four patients were men and 12 were women, and the average age of the patients was 58.8?years (range, 37?C72?years). In the TPF group, patients received CCRT with the TPF regimen [docetaxel (50?mg/m2, day 1), CDDP (60?mg/m2, day 4) and a continuous 5-FU infusion (600?mg/m2/day, days 1?C5)]. In the PFML group, patients received CCRT with the PFML regimen [CDDP (60?mg/m2, day 4), a continuous 5-FU infusion (600?mg/m2/day, days 1?C5), methotrexate (30?mg/m2, day 1) and leucovorin (10?mg/m2/day, days 1?C5)]. The total radiation dose was between 66.6 and 70.2?Gy.Results
The overall 5-year survival rate was 64.6% in all patients, 68.6% in the resectable group and 47.4% in the unresectable group. The 5-year disease-specific survival rate was 72.2% in all patients, 78.1% in the resectable group and 47.7% in the unresectable group. Regarding clinical stage, the 5-year disease-specific survival rates were 91% in stage III, 72% in stage IVa and 44% in stage IVb.Conclusion
CCRT with TPF or PFML regimen for advanced oropharyngeal SCC is tolerable and effective, especially in patients with resectable disease. 相似文献9.
S. Fushida J. Kinoshita M. Kaji Y. Hirono F. Goda Y. Yagi K. Oyama Y. Sudo Y. Watanabe T. Fujimura 《Cancer chemotherapy and pharmacology》2013,71(5):1265-1272
Purpose
We designed a phase I/II trial of intraperitoneal (IP) docetaxel plus S-1 to determine the maximum tolerated dose (MTD) and recommended dose (RD) and to evaluate its efficacy and safety in gastric cancer patients with peritoneal carcinomatosis (PC).Methods
Patients with PC confirmed by laparoscopy or laparotomy received IP docetaxel on days 1 and 15 and S-1 (80 mg/m2) on days 1–14 every 4 weeks.Results
In the phase I part (n = 12), each cohort received escalating doses of docetaxel (35–50 mg/m2); the MTD was determined to be 50 mg/m2 and the RD was determined to be 45 mg/m2. Dose-limiting toxicities included grade 3 febrile neutropenia and grade 3 diarrhea. In the phase II part (n = 27), the median number of courses was 4 (range 2–11). The 1-year overall survival (OS) rate was 70 % (95 % confidence interval 53–87 %). The overall response rate was 22 % and peritoneal cytology turned negative in 18 of 22 (81 %) patients. The most frequent grade 3/4 toxicities included anorexia (19 %), neutropenia (7 %), and leukopenia (7 %).Conclusion
IP docetaxel plus S-1 is active and safety in gastric cancer patients with PC. 相似文献10.
Simon Pernot Emmanuel Mitry Emmanuelle Samalin Laetitia Dahan Cécile Dalban Marc Ychou Jean-François Seitz Hajer Turki Thibault Mazard Aziz Zaanan Céline Lepère Jean-Nicolas Vaillant Bruno Landi Philippe Rougier Julien Taieb 《Gastric cancer》2014,17(2):341-347
Background
Docetaxel–cisplatin-5-FU chemotherapy is superior to 5-FU-cisplatin in terms of response rate and survival in advanced gastric cancer (AGC), but is more toxic. Oxaliplatin is better tolerated than cisplatin, which it can effectively replace in this setting. We hypothesize that incorporating docetaxel into a simplified FOLFOX regimen should be a tolerable and effective option in first-line treatment of AGC.Methods
Data were collected at six French centers from patients with metastatic or local AGC who received docetaxel, fluorouracil, leucovorin, or oxaliplatin (TEF) as first-line treatment. TEF was administered as follows: docetaxel (50 mg/m2), oxaliplatin (85 mg/m2), and leucovorin (40 mg/m2) on day 1, and 5-FU continuous infusion for 48 h (2400 mg/m2) every 2 weeks.Results
Forty-one patients were enrolled. Performance status was grade 0 and 1 in respectively 27 and 58 % of patients; 17 patients had adenocarcinoma of the gastroesophageal junction; 37 patients had metastatic disease, 22 had a poorly differentiated or diffuse type. Objective response rate was 66 %, with a complete response in two patients (5 %). Median progression-free survival and overall survival were respectively 6.3 and 12.1 months. Tolerability was acceptable with no treatment-related deaths. The most frequent grade 3–4 toxicities were neutropenia (30 %) and neuropathy (12.5 %). Curative intent surgery after response to TEF was performed in seven patients (17 %).Conclusion
TEF is an effective first-line treatment with an acceptable toxicity profile for patients with AGC. It may allow curative resection in initially unresectable patients. TEF should now be evaluated in prospective randomized trials. 相似文献11.
Qiang Lin Yue’e Liu Chuilin Chang Na Wang Jingmei Fu Xiaocang Ren Xueji Chen Jing Hu Yansheng Tian Zhijun Guo Yannan Zhao 《中德临床肿瘤学杂志》2012,11(1):6-10
Objective
Capecitabine combined with docetaxel have demonstrated antitumor synergy for non-small cell lung cancer (NSCLC). Due to absence of phase I trial in China, we conducted this study to define the maximum-tolerated dose (MTD) of capecitabine with fixed docetaxel for Chinese patients with previously treated NSCLC.Methods
Previously treated patients with NSCLC were entered into this study. Escalating doses of capecitabine with fixed docetaxel were administered in a modified Fibonacci sequence. The initial doses were capecitabine 625 mg/m2, bid, on days d5?Cd18, and docetaxel 30 mg/m2 on days 1 and 8, respectively. The regimen was repeated every 21 days. If no dose-limiting toxicity (DLT) was observed, the next dose level was applied. The procedures were repeated until DLT appeared. The MTD was declared to be one dose level below the level at which DLT appeared.Results
Eighteen patients received 67 cycles at capecitabine of level I (1250 mg/m2, divided into 625 mg/m2, bid) and level II (1500 mg/m2, 750 mg/m2, bid). The most common toxicities were neutropenia, hand and feet syndrome, fatigue and nausea. Eight DLTs occurred in 5 patients in the whole group, including 1 DLT in dose level I and 7 DLTs in dose level 2. Since 4 of 6 patients in level II experienced DLTs, we declared thus level I was MTD.Conclusion
MTD of our phase I trial was capecitabine of 1250 mg/m2/d combined with docetaxel of 30 mg/m2/wk. This combination regimen was well tolerated for previously treated patients with NSCLC. The efficacy of this schedule is currently being further evaluated in a prospective phase II trial. 相似文献12.
Luis E. Raez Kyriakos Papadopoulos Alejandro D. Ricart E. Gabriella Chiorean Robert S. DiPaola Mark N. Stein Caio M. Rocha Lima James J. Schlesselman Khaled Tolba Virginia K. Langmuir Stewart Kroll Donald T. Jung Metin Kurtoglu Joseph Rosenblatt Theodore J. Lampidis 《Cancer chemotherapy and pharmacology》2013,71(2):523-530
Purpose
This phase I trial was initiated to evaluate the safety, pharmacokinetics (PK) and maximum tolerated dose (MTD) of the glycolytic inhibitor, 2-deoxy-d-glucose (2DG) in combination with docetaxel, in patients with advanced solid tumors.Methods
A modified accelerated titration design was used. 2DG was administered orally once daily for 7 days every other week starting at a dose of 2 mg/kg and docetaxel was administered intravenously at 30 mg/m2 for 3 of every 4 weeks beginning on day 1 of week 2. Following the completion of dose escalation, cohorts of patients were then treated with 2DG for 21 days or every day of each 4-week cycle for up to 12 cycles.Results
Thirty-four patients were enrolled: 21 on every other week, 6 on a 21 of 28-day cycle and 7 on the continuous 2DG dosing schedule. There were no dose-limiting toxicities which met the MTD criteria. The most common adverse events were fatigue, sweating, dizziness and nausea mimicking the hypoglycemic symptoms expected from 2DG administration. Therefore, 63 mg/kg was selected as the clinically tolerable dose. The most significant adverse effects noted at 63–88 mg/kg doses were reversible hyperglycemia (100 %), gastrointestinal bleeding (6 %) and reversible grade 3 QTc prolongation (22 %). Eleven patients (32 %) had stable disease, 1 patient (3 %) partial response and 22 patients (66 %) progressive disease as their best response. There was no PK interaction between 2DG and docetaxel.Conclusion
The recommended dose of 2DG in combination with weekly docetaxel is 63 mg/kg/day with tolerable adverse effects. 相似文献13.
Lee DH Kim HT Han JY Lee SY Yoon SJ Kim HY Lee JS 《Cancer chemotherapy and pharmacology》2008,61(1):83-88
Purpose
This phase II study assessed the efficacy and toxicity profile of a modified weekly irinotecan and cisplatin for chemotherapy-naïve patients with metastatic/recurrent esophageal squamous cell carcinoma (SQCC).Methods
The eligibility criteria included histologically confirmed esophageal SQCC, no prior chemotherapy, adequate organ functions and written informed consent. Patients received irinotecan 65 mg/m2 plus cisplatin 30 mg/m2 on days 1 and 8, every 3 weeks.Results
Thirty-two patients were assessed for response and toxicity. Ten patients achieved a partial response (31.3%; 95% CI, 16.0–50.0%). With a median follow-up of 19.0 months, median progression-free and overall survival was 4.4 and 9.6 months, respectively, with a 1-year survival rate of 27.4%. Grade (G) 3/4 neutropenia was observed in 50.0% of the patients, which was the most common cause of dose reduction or therapy delay. G3 non-hematologic toxicity included seven (21.9%) asthenias, four (12.5%) diarrheas, and one (3.1%) nausea/vomiting, but no G4 non-hematologic toxicity was observed.Conclusions
This modified weekly irinotecan and cisplatin failed to ameliorate hematologic toxicity and to improve efficacy. However, easy administration and favorable non-hematologic toxicity as well as modest anti-tumor activity against metastatic or recurrent esophageal SQCC can make this regimen a potential treatment option, given the complexity of administration and toxicity of conventional infusional 5-FU and cisplatin. 相似文献14.
Francisco Robert Alan Sandler Joan H. Schiller Glenn Liu Karen Harper Lev Verkh Xin Huang Jennifer Ilagan Lesley Tye Richard Chao Anne M. Traynor 《Cancer chemotherapy and pharmacology》2010,66(4):669-680
Purpose
Sunitinib in combination with docetaxel enhances antitumor activity in xenograft models of human breast and non-small cell lung cancer. We assessed the maximum tolerated doses (MTDs), safety, pharmacokinetic profiles, and preliminary efficacy of sunitinib plus docetaxel in patients with advanced solid tumors.Methods
In this phase I study, successive patient cohorts received sunitinib 25, 37.5, or 50 mg/day for 4 weeks of a 6-week cycle (Schedule 4/2, 4 weeks on, 2 weeks off) or for 2 weeks of a 3-week cycle (Schedule 2/1, 2 weeks on, 1 week off) with docetaxel 60 or 75 mg/m2 IV q21d to determine the MTDs of this treatment combination.Results
Fifty patients enrolled: 10 on Schedule 4/2 and 40 on Schedule 2/1. MTDs were established as sunitinib 25 mg on Schedule 4/2 with docetaxel 60 mg/m2 q21d, and as sunitinib 37.5 mg on Schedule 2/1 with docetaxel 75 mg/m2 q21d. On Schedule 2/1, the most frequent dose-limiting toxicity was neutropenia (±fever; grade [G]3/4, n = 5) and the most common G3/4 non-hematologic adverse event (AE) was fatigue (G3, n = 8). Hematologic AEs were managed with growth factor support in 11 of 23 (48%) patients treated at Schedule 2/1 MTD. Three patients achieved a partial response at the Schedule 2/1 MTD. There were no pharmacokinetic drug–drug interactions with either schedule.Conclusions
Oral sunitinib 37.5 mg/day on Schedule 2/1 with docetaxel 75 mg/m2 IV q21d is a clinically feasible regimen with a manageable safety profile, no pharmacokinetic drug–drug interactions, and shows antitumor activity in patients with advanced solid tumors. 相似文献15.
Ritesh Rathore Ariel Birnbaum Bharti Rathore Thomas DiPetrillo Teresa Kennedy Neal Ready 《Cancer chemotherapy and pharmacology》2010,66(6):1013-1017
Purpose
A phase I study was performed to determine the maximally tolerated dose of carboplatin, ifosfamide, and docetaxel in advanced head and neck cancers.Methods
Carboplatin (week 1) was administered with weekly docetaxel and ifosfamide for 3 weeks in an every 4-week cycle. Restaging was done after two cycles, while dose level escalation was done in cohorts of three patients.Results
Fifteen patients (recurrent/metastatic disease, n = 8; bulky locally advanced disease, n = 7) were enrolled. No dose-limiting toxicities were observed. Toxicities included grade 3 neutropenia and anemia (n = 2, each), and grade 2 thrombocytopenia (n = 3). The final level of carboplatin AUC = 6 (week 1) with docetaxel 30 mg/m2 per week and ifosfamide 1,000 mg/m2 per week was chosen for further evaluation.Conclusions
This novel regimen of carboplatin with weekly docetaxel and ifosfamide has a favorable toxicity profile and is active in this setting. Phase II study results are awaited. 相似文献16.
Cui Chen Feng-hua Wang Xin An Hui-yan Luo Zhi-qiang Wang Ying Liang Le Zhang Yu-hong Li 《Cancer chemotherapy and pharmacology》2013,71(2):371-378
Purpose
Platinum-based chemotherapy is the recognized first-line treatment for metastatic nasopharyngeal carcinoma (NPC). However, no standard treatment regimens have been established. This phase II study was designed to evaluate the efficacy and safety of a paclitaxel, cisplatin and 5-FU combination in metastatic and/or recurrent NPC.Methods
Patients with evaluable metastatic and/or recurrent NPC were entered into this study. Treatment consisted of paclitaxel at a dose of 135 mg/m2 on day 1, cisplatin 25 mg/m2/day from day 1 to day 3 and 5-FU-continuous infusion for 120 h at a variable dosage from 600 to 1,000 mg/m2/day according to prior radiation. This regimen was repeated every 3 weeks.Results
A total of 95 patients were enrolled; 92 patients were evaluable for response. The overall response and disease control rates were 78.9 and 93.6 %, respectively. At a median follow-up of 24.8 months, the respective median overall survival (OS) and progression-free survival were 22.7 months (95 % CI 18.6–26.9 months) and 8.6 months (95 % CI 7.7–9.5 months). Toxicities were moderate and manageable. Grade 3/4 toxicities included leucopenia (14.7 %), neutropenia (17.9 %), anemia (3.2 %), thrombocytopenia (6.4 %), nausea (4.2 %), vomiting (9.5 %), stomatitis (9.5 %), diarrhea (3.2 %), aminotransferase (2.2 %) and sensory neuropathy (3.2 %).Conclusion
Triplet combination chemotherapy with paclitaxel, cisplatin and 5-FU is an effective and safe option in the front-line treatment for recurrent and/or metastatic NPC. The encouraging results with high response rate and long OS suggest that this regimen might be especially considered where tumor shrinkage is required. 相似文献17.
A phase I trial of S-1 with concurrent radiotherapy in patients with locally recurrent rectal cancer
Hitoshi Wada Kenji Nemoto Takuma Nomiya Misako Murakami Motohisa Suzuki Yuuki Kuroda Mayumi Ichikawa Ibuki Ota Yasuhito Hagiwara Hisanori Ariga Ken Takeda Kenji Takai Keisuke Fujimoto Masahiro Kenjo Kazuhiko Ogawa 《International journal of clinical oncology / Japan Society of Clinical Oncology》2013,18(2):273-278
Background
The purpose of this phase I trial of S-1 chemotherapy in combination with pelvic radiotherapy for locally recurrent rectal cancer was to determine the maximum tolerated dose (MTD), recommended dose (RD), and dose-limiting toxicity (DLT) of S-1.Methods
We enrolled 9 patients between April 2005 and March 2009. Radiotherapy (total dose, 60 Gy in 30 fractions) was given to the gross local recurrent tumor and pelvic nodal metastases using three-dimensional radiotherapy planning. We administered oral S-1 twice a day on days 1–14 and 22–35 during radiotherapy. The dose of S-1 was initially 60 mg/m2/day and was increased to determine the MTD and RD for this regimen.Results
DLT appeared at dose level 2 (70 mg/m2/day) in 2 patients, who experienced grade 3 enterocolitis and consequently required suspension of S-1 administration for longer than 2 weeks. Hematological toxicity was mild and reversible. At the initial evaluation, complete regression and partial regression were seen in 1 patient (11%) and 2 patients (22%), respectively.Conclusion
This phase I trial of S-1 chemotherapy with pelvic radiotherapy for locally recurrent rectal cancer revealed that the MTD for S-1 was 70 mg/m2/day and the RD was 60 mg/m2/day. 相似文献18.
Minghua Bai Baofeng Wang Xijing Wang Hongbing Ma Yali Wang Zhongwei Wang 《中德临床肿瘤学杂志》2013,12(8):361-364
Objective
This randomized controlled clinical study was to assess and compare the efficacy and safety of two chemoradiotherapy regimens [cisplatin + 5-fluorouracil + 3 dimensional conformal radiation therapy (3DCRT) and cisplatin + weekly docetaxel + 3DCRT] in patients with locally advanced esophageal squamous cell carcinoma.Methods
A total of seventy-four patients with clinical stages IIB to IIIB esophageal squamous cell carcinoma were enrolled. Chemotherapy for PF group comprised 5-fluorouracil at days 1–5 (250 mg/m2/d) and cisplatin (20 mg/m2) at days 1–3 of every 28-day cycle; full treatment course included 2 cycles. Chemotherapy for DP group comprised docetaxel (20 mg/m2) and cisplatin (20 mg/m2) at days 1, 8, 15, 22, 29, and 36. Both groups treated with concurrent 60 Gy 3DCRT at 200 cGy/d.Results
Seventy-four patients were enrolled and 71 completed the planned treatment, with a follow-up rate of 95.94%. Short-term curative effect was not statistically significant between the two groups (P = 0.471). The 2-year survival rates were 65.7% and 61.1%, respectively (P = 0.806), 5 years survival rates were 34.29% and 27.78%, respectively (P = 0.221), and there was no significant difference by Fisher test (P = 0.734). As common side effects, incidence rates of radioactive esophagitis and hematological toxicity were lower in DP group.Conclusion
For locally advanced esophageal cancer patients, current chemoradiotherapy with chemotherapy regimen of weekly docetaxel plus cisplatin has equal curative effect with 5-fluorouracil plus cisplatin, but well-tolerated by reducing side effects such as radioactive esophagitis and bone marrow suppression. 相似文献19.
Zaniboni A Aitini E Barni S Ferrari D Cascinu S Catalano V Valmadre G Ferrara D Veltri E Codignola C Labianca R 《Cancer chemotherapy and pharmacology》2012,69(6):1641-1645
Purpose
The purpose of the present study was to evaluate the activity and the tolerability of the FOLFIRI regimen, administered as second-line chemotherapy in patients with locally advanced or metastatic pancreatic cancer after the failure of a gemcitabine-based regimen.Methods
Patients with locally advanced/metastatic disease who received a first-line chemotherapy (one line only) with gemcitabine ± platinoid (cisplatin, oxaliplatin) and who had measurable disease conform with the RECIST criteria were eligible for the study. FOLFIRI consists of irinotecan 180 mg/m2 iv on day 1, leucovorin (l-form) 200 mg/m2 iv on day 1 and 2, 5-FU 400 mg/m2 iv bolus on days 1 and 2, and 5-FU 600 mg/m2 iv by ci for 22 h on days 1 and 2, repeated every 2 weeks. The primary end point was the response rate.Results
Among the 50 enrolled patients, 4 partial responses (PR) (8 %) and 14 stable diseases were observed, for a disease control rate of 18/50 (36 %). Forty-one patients (82 %) have been pretreated with cisplatin/oxaliplatin+gemcitabine as first-line chemotherapy. The median progression-free and overall survivals were 3.2 and 5 months, respectively. The 6-month survival rate was 32 %. Grade 3–4 neutropenia and diarrhea occurred in 10 (20 %) and 6 (12 %) patients, respectively.Conclusion
The FOLFIRI regimen showed a modest clinical activity in this quite heavily pretreated patients’ population with locally advanced or metastatic pancreatic cancer with a manageable toxicity profile. 相似文献20.
Woo Kyun Bae Jun Eul Hwang Hyun Jeong Shim Sang Hee Cho Joon Kyoo Lee Sang-Chul Lim Woong-Ki Chung Ik-Joo Chung 《Cancer chemotherapy and pharmacology》2010,65(3):589-595