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1.
Sakakibara-Konishi J Oizumi S Kinoshita I Shinagawa N Kikuchi J Kato M Inoue T Katoh N Onimaru R Shirato H Dosaka-Akita H Nishimura M 《Lung cancer (Amsterdam, Netherlands)》2011,74(2):248-252
Introduction
Although paclitaxel with carboplatin and thoracic radiotherapy has improved survival for patients with locally advanced unresectable non-small cell lung cancer (NSCLC), the optimal dose of paclitaxel has not been well defined in Japan. This study was conducted to determine the maximum tolerated dose (MTD) and recommended dose (RD) of paclitaxel in combination with carboplatin and concurrent real-time tumor-tracking thoracic radiation therapy (thoracic RTRT).Patients and methods
Previously untreated patients with histologically confirmed, locally advanced unresectable NSCLC were eligible. Before treatment, gold markers were inserted into the lung and the mediastinum of all patients. RTRT comprised a total of 66 Gy at 2 Gy/fraction, 5 days/week, for 7 weeks. Patients received paclitaxel at a starting dose of 40 mg/m2 followed by carboplatin at a fixed area under the curve (AUC) of 2, as a weekly regimen with RTRT. The dose of paclitaxel was escalated by 5 mg/m2 per level.Results
Eight patients with locally advanced unresectable NSCLC were enrolled and treated with two dose levels of paclitaxel (40 mg/m2 and 45 mg/m2), carboplatin (AUC = 2) and RTRT. No dose limiting toxicities (DLTs) were observed at Level 1 (paclitaxel, 40 mg/m2 and carboplatin, AUC = 2). At Level 2 (paclitaxel, 45 mg/m2 and carboplatin, AUC = 2), two of five patients experienced DLTs, in the form of esophagitis and discontinuation of chemotherapy more than twice. The MTD and RD of paclitaxel were thus defined as 45 mg/m2 and 40 mg/m2, respectively.Conclusions
This phase I study was well tolerated and the RD of paclitaxel and carboplatin with RTRT is 40 mg/m2 at AUC = 2, respectively. Further studies are warranted to evaluate the efficacy of this regimen. 相似文献2.
Watanabe Y Nakai H Shimaoka M Tobiume T Tsuji I Hoshiai H 《International journal of clinical oncology / Japan Society of Clinical Oncology》2006,11(4):309-313
Background Although the prognostic advantages of concurrent cisplatin (CDDP) chemoradiation therapy (CCRT), for uterine cervical cancer
(UCC) has been demonstrated, the feasibility of concurrent CDDP administration has not yet been evaluated. We determined the
optimal CDDP dose for both weekly and monthly schedules during primary and adjuvant CCRT in patients with UCC.
Methods The study was conducted as a phase I, dose-escalation trial. Concurrent CDDP was started at the dose of 30 mg/m2 for the weekly schedule and at 50 mg/m2 for the monthly schedule, and the doses were steadily escalated to the maximum tolerated dose (MTD).
Results A total of 45 patients with UCC (25 receiving primary CCRT and 20 receiving adjuvant CCRT) were entered in the study. In both
the primary and adjuvant CCRT patients, the MTD was observed to be 40 mg/m2 for the weekly schedule and 80 mg/m2 for the monthly schedule. Dose-limiting toxicity was observed in 10 patients (granulocytopenia in 9 patients and diarrhea
in 1 patient). Disease recurrence was confirmed in 6 patients in the primary CCRT group during a mean follow-up period of
22.4 ± 13.2 months, and in patients 3 in the adjuvant CCRT group during a mean follow-up period of 17.7 ± 6.8 months.
Conclusion For Japanese patients with UCC receiving primary or adjuvant CCRT therapy, the recommended CDDP dose was determined to be
30 mg/m2 for the weekly schedule and 75 mg/m2 for the monthly schedule. 相似文献
3.
Ian N. Olver Lorraine K. Webster Michael J. Millward Kerrie H. Stokes James F. Bishop 《Cancer chemotherapy and pharmacology》1995,37(1-2):79-85
A total of 18 patients received 6-week ambulatory infusions of carboplatin in groups at dose levels of 14, 28, 35 and 42 mg/m2 per day. The dose-limiting toxicity was myelosuppression. At 42 mg/m2, three of four patients had WHO grade 4 and one of four had grade 3 neutropenia, whereas two patients had grade 3 thrombocytopenia. At 35 mg/m2, two of five patients had grade 3 neutropenia, whereas one had grade 4 and two had grade 3 thrombocytopenia. Non-hematological toxicities were predominantly gastrointestinal, with 3 of 18 patients experiencing grade 3 emesis. Total and ultrafiltrable platinum (UFPt) were assayed by flameless atomic absorption spectrometry in weekly and post-infusion plasma and urine samples. In plasma, levels of total platinum increased throughout the infusion, and the protein binding slowly increased from 60% platinum bound at week 1 to 90% bound by week 4. Although the UFPt level reached a steady state within 1 week, the concentration did not increase with the dose level, remaining at a mean value of 0.58±0.24 M. Renal excretion of platinum accounted for 70±12% of the dose at steady state. There was a high inter-patient variability in both total body clearance of UFPt (range, 83–603 ml/min) and renal clearance (range, 67–390 ml/min). A terminal elemination half-life of 13–27 h was noted for post-infusion UFPt. Neutropenia was linearly related to the total daily carboplatin dose, but neither neutropenia nor thrombocytopenia could be related to steady-state UFPt or the UFPt area under the concentration-time curve (AUC). The recommended dose for phase II studies is 28 mg/m2 per day. 相似文献
4.
Etienne Chatelut Christine Chevreau Valérie Brunner Mathilde Martinez Georges Houin Roland Bugat Pierre Canal 《Cancer chemotherapy and pharmacology》1995,35(5):391-396
Carboplatin is an alternative for cisplatin in the treatment of urothelial cancers. A pharmacologically guided phase I study
of carboplatin in combination with methotrexate (30 mg/m2) and vinblastine (4 mg/m2) was conducted in ten patients by increment of the area under the plasma concentration versus time curve (AUC) for ultrafilterable
carboplatin using the Calvert formula. The maximal tolerated AUC was 5 mg ml-1 min, with neutropenia being the dose-limiting toxicity. There was a significant linear correlation between the percentage
of decrease in neutrophil count and the carboplatin AUC. Determination of the glomerular filtration rate by the isotopic method
allowed us to adapt the dose of carboplatin given to patients suffering from urothelial cancer, who frequently have impaired
renal function. The recommended AUC for phase II study is 4 mg ml-1 min.
Received: 9 May 1994/Accepted: 16 August 1994 相似文献
5.
Purpose: This phase I study aimed to establish the dose for phase II trials of a dose-intense outpatient regimen of ambulatory carboplatin
and oral etoposide. Patients and Methods: Cohorts of three patients received escalating doses of carboplatin 15, 20, and 23 mg/m2/day as a 3-week continuous ambulatory infusion with oral etoposide initially at 50 mg/day. Patients entered had prostate,
colon, head and neck, breast, unknown primary cancers and mesothelioma. Results: At 23 mg/m2 of carboplatin, two patients had WHO grade 3 lethargy and myelosuppression, which were the dose-limiting toxicities. Six
patients were entered at the dose recommended for phase II studies, carboplatin 20 mg/m2/day and etoposide 50 mg/day for 21 days repeated every 6 weeks. This was well tolerated except for one patient with multiple
bone metastases from prostate cancer experiencing grade 4 myelosuppression and a single patient with grade 3 constipation.
Seven patients with hormone-resistant prostate cancer were entered into the study, one at 15 mg/m2, four at 20 mg/m2 and two at 23 mg/m2 of carboplatin, and received a median of four cycles of treatment. The only responses were seen in prostate cancer where
there were two partial responses in patients with soft tissue predominant disease. Five patients who could be evaluated with
initially elevated PSA exhibited falls of ≥50% after receiving the chemotherapy. All but one patient with prostate cancer
experienced significant reduction in pain levels. The median time to progression of the patients with prostate cancer was
4 months. Conclusions: Ambulatory infusion carboplatin and oral etoposide is a tolerable dose- intense outpatient regimen which warrants further
testing in phase II trials including hormone-resistant prostate cancer.
Received: 13 March 2000 / Accepted: 26 May 2000 相似文献
6.
Hanxi Zhao Wanqi Zhu Peng Xie Huiqin Li Xiqin Zhang Xiaorong Sun Jinming Yu Ligang Xing 《Radiotherapy and oncology》2014
Background and purpose
Patients with unresectable stage III non-small-cell lung cancer receiving concurrent chemoradiotherapy often develop esophagitis that may lead to unplanned treatment interruptions, which may severely reduce rates of locoregional tumor control and survival. No effective treatment that would reduce the incidence and severity of this complication has been identified up to now. Although acceleration of normal tissue protection using epigallocatechin-3-gallate (EGCG) has been reported, its actual clinical practicability remains obscure.Methods and materials
This is a phase I study of EGCG in combination with standard chemoradiation in surgically unresectable stage III non-small-cell lung cancer. Chemotherapy (cisplatin and etoposide) was given concurrently with radiation. EGCG solution was swallowed three times a day after the occurrence of grade 2 esophagitis at six concentration levels and dose escalation followed a standard phase I design. Esophageal toxicity and patient-reported pain was recorded weekly.Results
Twenty-four patients with AJCC stage IIIA (six) and IIIB (eighteen) completed the course of therapy. Twelve had squamous histology, ten adenocarcinoma, and two not specified. Patients were treated in six cohorts at six dose levels of EGCG. RT was not interrupted with a median dose of 64 Gy. There were no dose-limiting toxicities reported in all EGCG dosing tiers. Dramatic regression of esophagitis to grade 0/1 was observed in 22 of 24 patients, whereas grade 2 esophagitis persisted in 2 of 24 patients at the end of radiotherapy. The pain score was also reduced from a mean of 4.58 (N = 24), 1.29 (N = 24), 1.42 (N = 24), 0.96 (N = 23) to 1.13 (N = 16) every week in turn.Conclusion
We conclude that the oral administration of EGCG is feasible, safe and effective. The phase II recommended concentration is 440 μmol/L. 相似文献7.
S. Pignata P. Frezza S. Tramontana F. Perrone R. Tambaro G. Casella E. Ferrari F. Iodice R. De Vivo P. Ricchi F. Tramontana G. Silvestro 《Annals of oncology》2000,11(4):455-459
Background.Cisplatin and paclitaxel are active in cervical cancerand both are able to potentiate the effects of radiotherapy. In this study weevaluated the maximum-tolerated dose (MTD) of paclitaxel in combination witha fixed dose of cisplatin when given weekly concurrently with pelvicradiotherapy to patients with carcinoma of the cervix uteri.
Patients and methods:Eighteen patients with cervical cancer wereenrolled in this study. Cisplatin (30 mg/m2) and paclitaxel(starting dose 40 mg/m2; 5 mg/m2 escalation per level)were given on day 1 of radiotherapy and then weekly for six times.Radiotherapy was given to the pelvis with a four-field box technique for fivedays each week. Patients received 65 Gy in 1.8 Gy fractions. Cohorts of threepatients were enrolled at each level and three further patients were includedif one or two dose-limiting severe adverse events (SAE) were recorded. SAE wasdefined as grade 3 or 4 nonhematologic toxicity, excluding nausea or vomitingand alopecia, grade 4 neutropenia or thrombocytopenia, and prolonged (>1week) neutropenia or thrombocytopenia.
Results:Four levels were studied (paclitaxel 40, 45, 50, 55mg/m2) with three, five, four and six patients enrolled,respectively. The MTD of paclitaxel was found at 50 mg/m2/wk andcisplatin 30 mg/m2/wk. Diarrhea was the dose-limiting toxicity.Thirteen patients were evaluable for response: seven complete and five partialresponses were obtained with an overall response rate of 92.3%.
Conclusions:The MTD of paclitaxel is 50 mg/m2/wk whenassociated to cisplatin 30 mg/m2/wk and concurrent pelvicradiotherapy. Diarrhea is the dose limiting side effect. Preliminary datasuggest that concurrent chemoradiotherapy with paclitaxel and cisplatin couldbe a very active treatment for patients with locally advanced carcinoma of thecervix. 相似文献
8.
Herrera FG Chan P Doll C Milosevic M Oza A Syed A Pintilie M Levin W Manchul L Fyles A 《International journal of radiation oncology, biology, physics》2007,67(1):97-103
PURPOSE: To evaluate the toxicity and effectiveness of celecoxib in combination with definitive chemoradiotherapy (CRT) in women with locally advanced cervical cancer. METHODS AND MATERIALS: Thirty-one patients were accrued to a phase I-II trial of celecoxib 400 mg by mouth twice per day for 2 weeks before and during CRT. Tumor oxygenation (HP(5)) and interstitial fluid pressure (IFP) were measured before and 2 weeks after celecoxib administration alone. The median follow-up time was 2.7 years (range, 1.1-4.4 years). RESULTS: The most common acute G3/4 toxicities were hematologic (4/31, 12.9%) and gastrointestinal (5/31, 16.1%) largely attributed to chemotherapy. Late G3/4 toxicity was seen in 4 of 31 patients (13.7% actuarial risk at 2 yr), including fistulas in 3 patients (9.7%). Within the first year of follow-up, 25 of 31 patients (81%) achieved complete response (CR), of whom 20 remained in CR at last follow-up. After 2 weeks of celecoxib administration before CRT, the median IFP decreased slightly (median absolute, -4.6 mm Hg; p = 0.09; relative, -21%; p = 0.07), whereas HP(5) did not change significantly (absolute increase, 3.6%; p = 0.51; median relative increase, 11%; p = 0.27). No significant associations were seen between changes in HP(5) or IFP and response to treatment (p = 0.2, relative HP(5) change and p = 0.14, relative IFP change). CONCLUSIONS: Celecoxib in combination with definitive CRT is associated with acceptable acute toxicity, but higher than expected late complications. Celecoxib is associated with a modest reduction in the angiogenic biomarker IFP, but this does not correspond with tumor response. 相似文献
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10.
Takaki Yoshikawa Akira Tsuburaya Naoki Hirabayashi Kazuhiro Yoshida Naoki Nagata Yasuhiro Kodera Naoto Takahashi Koji Oba Masayuki Kimura Satoshi Ishikura Yumi Miyashita Junichi Sakamoto 《Cancer chemotherapy and pharmacology》2009,64(6):1071-1077
Purpose To establish the maximum tolerated dose and dose-limiting toxicity of chemoradiation with paclitaxel (PTX) and cisplatin (CDDP)
for patients with local symptoms due to unresectable primary advanced or locally recurrent gastric adenocarcinoma located
at left-upper abdomen.
Methods Chemotherapy consisted of PTX at escalating doses of 40–80 mg/m2 per day and CDDP at escalating doses of 20–25 mg/m2 per day on days 1, 15, and 29. Concurrent radiation was administered up to a dose of 45 Gy for 5 weeks.
Results A total of nine patients were enrolled, of which six were into level 1 (PTX 60 mg/m2 and CDDP 20 mg/m2) and three into level −1 (PTX 50 mg/m2 and CDDP 20 mg/m2). At level 1, one patient developed grade 3 fatigue, and the other experienced grade 5 DIC, grade 5 pneumonia, grade 4 thrombocytopenia,
grade 3 hyponatremia, and grade 3 esophagitis as dose-limiting toxicities. A palliative effect was observed in eight of nine
patients; six of six patients at level 1 and two of three at level −1.
Conclusion PTX 50 mg/m2 and CDDP 20 mg/m2 given biweekly with concurrent radiation therapy of 45 Gy were well tolerated. 相似文献
11.
Tassinari D Drudi G Panzini I Pasini G Arcangeli V Fochessati F Gianni L Mianulli AM Oliverio G Pasquini E Sartori S Ravaioli A 《International journal of clinical oncology / Japan Society of Clinical Oncology》2001,6(6):279-283
Background. Some trials have suggested that the combination of gemcitabine and platinum compounds can have a synergistic effect on several
solid tumors, but, at present, the data concerning carboplatin-gemcitabine combinations are not sufficient to allow the planning
of phase II trials. The present phase I trial was planned to define the maximum tolerated dose and the dose-limiting toxicity
of a carboplatin-gemcitabine combination.
Methods. Thirty-two patients with advanced, pretreated solid tumors were treated with carboplatin on day 1 and gemcitabine on days
1, 8, and 15 every 28 days. The starting doses of carboplatin and gemcitabine were 3.5 mg/ml per min (area under the curve;
AUC), and 600 mg/m2, respectively. The doses of the two agents were alternately increased to 4, 4.5, and 5 mg/ml per min and to 800 and 960 mg/m2, respectively. At each dose level, three patients were initially enrolled. If one of them experienced grade IV hematological
toxicity or grade III–IV nonhematological toxicity (with the exception of alopecia), an additional three patients were enrolled
at the same dose level. If two or more patients experienced grade IV hematological toxicity or grade III–IV non-hematological
toxicity (with the exception of alopecia), the maximum tolerated dose was considered to have been reached, and the dose below
this was recommended for further studies. All patients were evaluated weekly for toxicity and after every two courses of chemotherapy
for response.
Results. Dose-limiting toxicity was hematological, and the maximum tolerated doses were 4.5 mg/ml per min for carboplatin and 800
mg/m2 for gemcitabine. The activity of the carboplatin/gemcitabine combination was encouraging, with a 21.9% response rate (7/32),
three complete disease regressions, and a median time to progression of 30 weeks. The gemcitabine doses of day 15 or days
8 and 15 were omitted for hematological toxicity in 57 (50%) and 17 (14.9%) courses of chemotherapy, while no courses of chemotherapy
were delayed for grade III–IV hematological or nonhematological toxicity.
Conclusion. The maximum tolerated doses suggested by this trial are lower than those in other similar phase I trials, but they are consistent
with those reported by most of the trials investigating gemcitabine either in combination with cisplatin or in heavily pretreated
patients. Carboplatin 4.5 mg/ml per min on day 1 plus gemcitabine 800 mg/m2 on days 1, 8, and 15 every 28 days may represent a promising schedule for further phase II trials.
Received: January 29, 2001 / Accepted: September 13, 2001 相似文献
12.
Fakih MG Rajput A Yang GY Pendyala L Toth K Smith JL Lawrence DD Rustum YM 《International journal of radiation oncology, biology, physics》2006,65(5):1462-1470
PURPOSE: We conducted a Phase I study to determine the maximum tolerated dose (MTD) of neoadjuvant capecitabine, oxaliplatin, and radiation therapy (RT) in Stage II to III rectal adenocarcinoma. METHODS AND MATERIALS: Capecitabine was given orally twice daily Monday through Friday concurrently with RT. Oxaliplatin was given i.v. once weekly x 5 (for 5 weeks) starting the first day of RT. RT was given daily except on weekends and holidays at 1.8 Gy per fraction x 28. Escalation for capecitabine or oxaliplatin was to occur in cohorts of three patients until the maximum tolerated dose (MTD) was defined. Endorectal tumor biopsy samples were obtained before and on Day 3 of treatment to explore the effects of treatment on thymidine phosphorylase, thymidylate synthase, dihydropyrimidine dehydrogenase, DNA repair, and apoptosis. RESULTS: Twelve patients were enrolled on this study. Two of 6 patients at dose level (DL) 1 (capecitabine 825 mg/m2 orally (p.o.) given twice daily (b.i.d.); oxaliplatin 50 mg/m2/week) had a dose-limiting diarrhea. One of 6 patients at DL (-)1 (capecitabine 725 mg/m2 p.o., b.i.d.; oxaliplatin 50 mg/m2/week) experienced-dose-limiting diarrhea. Three of 11 patients who underwent resection had a complete pathologic response. No remarkable variations in rectal tumor biologic endpoints were noted on Day 3 of treatment in comparison to baseline. However, a higher apotosis index was observed at baseline and on Day 3 in complete pathologic responders (no statistical analysis performed). CONCLUSIONS: Capecitabine 725 mg/m2 p.o., twice daily in combination with oxaliplatin 50 mg/m2/week and RT 50.4 Gy in 28 fractions is the recommended dose for future studies. 相似文献
13.
Purpose: We conducted a phase I/II study in previously untreated patients with stage IIIB or IV non-small-cell lung cancer (NSCLC)
to: (1) determine the maximum tolerated dose (MTD) of cisplatin combined with a fixed schedule of ifosfamide and irinotecan
with rhG-CSF support; and (2) to determine the overall response rate and median survival of patients entered on this study.
Methods: Ifosfamide (1.5 g/m2) and irinotecan (60 mg/m2) were administered at fixed doses on days 1–4 and on days 1, 8 and 15, respectively. Cisplatin was given on day 1 at 60 mg/m2 and was increased in 10-mg/m2 increments. This regimen was repeated every 4 weeks. rhG-CSF (nartograstim) was administered subcutaneously at a dose of
1 μg/kg on days 5–18 except on the day of irinotecan treatment. Results: Between June 1995 and April 1998, 46 patients were registered onto this phase I/II study. The MTD of cisplatin was defined
according to toxicity and the dose during three courses was increased. Since at the 80 mg/m2 dose level more than one-third of the patients were treated with dose modification, the dose of 70 mg/m2 was recommended for phase II study. The dose-limiting toxicity was leukopenia. The overall response rate was 62.2% (95% CI
48.0–76.4%), the median response duration was 144 days, and the median survival time was 393 days. Conclusion: For phase II study, we recommend doses of cisplatin 70 mg/m2 on day 1 combined with ifosfamide and irinotecan with rhG-CSF support. Both the response rate and preliminary survival data
in this study suggest a high degree of activity of this combination in previously untreated NSCLC.
Received: 29 April 1999 / Accepted: 15 September 1999 相似文献
14.
15.
Czito BG Cohen DP Kelsey CR Lockhart AC Bendell JC Willett CG Petros WP D'Amico TA Truax R Hurwitz HI 《International journal of radiation oncology, biology, physics》2008,70(4):1066-1072
PURPOSE: Concurrent chemotherapy and radiation therapy (RT) are used to treat patients with esophageal cancer. The optimal combination of chemotherapeutic agents with RT is not well established. We evaluated the safety and preliminary efficacy of a combination of UFT/leucovorin, carboplatin, and paclitaxel with RT in a Phase I study of patients with advanced esophageal cancer. METHODS AND MATERIALS: Patients with squamous cell carcinoma or adenocarcinoma of the esophagus initially received UFT/leucovorin, carboplatin, and paclitaxel with RT (1.8 Gy daily to 45 Gy). After completion, the disease was restaged and patients were evaluated for surgery. Primary end points included determination of dose-limiting toxicities (DLTs) and a recommended Phase II dose. Secondary objectives included determination of non-DLTs, as well as preliminary radiographic and pathologic response rates. RESULTS: Twelve patients were enrolled (11 men, 1 woman). All were assessable for toxicity and efficacy. One of 6 patients at Dose Level 1 (UFT/leucovorin, 200/30 mg twice daily on RT days; carboplatin, area under the curve [AUC] 5, Weeks 1 and 4; paclitaxel, 175 mg/m2 Weeks 1 and 4) had a DLT (febrile neutropenia). Of these 6 patients, 4 underwent esophagectomy and none achieved a pathologic complete response. Six patients were then enrolled at Dose Level 2 (UFT/leucovorin, 300/30 mg in the morning and 200/30 mg in the evening on RT days; carboplatin, AUC 5, Weeks 1 and 4; paclitaxel, 175 mg/m2 Weeks 1 and 4). Two of 6 patients at Dose Level 2 developed DLTs (febrile neutropenia in both). Esophagectomy was performed in 3 patients, with 2 achieving a pathologic complete response. CONCLUSIONS: Maximum tolerated doses in this study were UFT/leucovorin, 200/30 mg twice daily on RT days; carboplatin, AUC 5, Weeks 1 and 4; and paclitaxel, 175 mg/m2 Weeks 1 and 4 when delivered with external RT. In this small study, this regimen appears active, but toxic. 相似文献
16.
Ichiki M Kawasaki M Takayama K Ninomiya K Kuba M Iwami F Miyazaki N Oishi K Takeo S Aizawa H Nakanishi Y 《Cancer chemotherapy and pharmacology》2006,58(3):368-373
Purpose: This multicenter phase II study was conducted to investigate the efficacy and safety of carboplatin in combination with paclitaxel administered according to a biweekly schedule as a first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC). Patients and methods: Eligibility criteria included histologically or cytologically confirmed NSCLC (stage IIIb or IV), no prior treatment, and measurable or evaluable disease. Paclitaxel (140 mg/m2) was administered intravenously on day 1, in combination with carboplatin at an area under the concentration time curve (AUC) of 3, every 2 weeks. Results: Seventy-four patients (45 men) with a median age of 62 years (range 40–74) and a median ECOG performance status of 1 (range 0–2) were enrolled. The response rate was 35.1% [95% confidence interval (CI): 24.4–47.1%], with 26 partial responses. The median survival was 357 days, and the median time to progression was 218 days. Toxicity was generally mild; National Cancer Institute-Common Toxicity Criteria (NCI-CTC) grades 3 and 4 neutropenia was observeded in 50.0% of the patients, and grades 3 and 4 nausea/vomiting in 4.1%. Conclusions: Biweekly carboplatin combined with paclitaxel demonstrated anti-tumor activity in advanced NSCLC, with response and survival rates similar to those of carboplatin combined with paclitaxel administered every 3 weeks but with a more favorable toxicity profile, and the present data indicate that the regimen is suitable for use on an outpatient basis. 相似文献
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18.
Ramanathan RK Fakih M Mani S Deutsch M Perez RP Ritter MA Eiseman JL Ivy SP Trump DL Belani CP Parise RA Potter DM Egorin MJ 《Cancer chemotherapy and pharmacology》2006,57(4):465-474
Purpose: To determine the maximum tolerated dose and dose-limiting toxicity (DLT) of the novel anticancer agent, motexafin gadolinium
(MGd), administered concurrently with radiation therapy (RT) in patients with locally advanced pancreatic or biliary tumors.
The pharmacokinetics of MGd were also evaluated. Methods: Cohorts of three to six patients were treated with escalating doses of MGd, administered three times per week for a total
of 16 doses concurrent with RT. The dose of RT was fixed at 5,040 cGy, and given in 28 fractions, from Monday to Friday of
every week. Plasma MGd concentrations were measured by high performance liquid chromatography. Results: Eight patients were treated at dose level 1 (2.9 mg/kg), with one DLT (grade 3 fever). Three patients were treated at dose
level 2 (3.6 mg/kg), and two DLTs were noted. One DLT was grade 3 nausea and vomiting (N/V), and the other was grade 3 skin
toxicity. The most common toxicity was N/V. There were no objective responses. The median survival was 6 months. The MGd plasma
concentration versus time profile in each patient was best fit by a two-compartment, open, linear model. There was minimal
accumulation of MGd in plasma with the three-times/week dosing schedule. Simulation of the time course of MGd in the peripheral
compartment indicated that maximal MGd concentrations of 1–2 μmol/kg occurred between 4 and 6 h after MGd infusion. Conclusion: Dose level 1 (2.9 mg/kg of MGd) is the recommended dose for combination with (RT) in phase II studies for locally advanced
pancreatic and biliary cancers. Patient tolerance might be improved by modification of the RT schedule and antiemetic prophylaxis. 相似文献
19.
Rosenthal DI Catalano PJ Haller DG Landry JC Sigurdson ER Spitz FR Benson AB 《International journal of radiation oncology, biology, physics》2008,72(1):108-113
PURPOSE: Oxaliplatin is a platinum analog and radiosensitizer active in colorectal cancer. We performed a Phase I trial to test the safety and preliminary efficacy of adding oxaliplatin to standard preoperative chemoradiation therapy for rectal cancer. METHODS AND MATERIALS: Eligible patients had T3 to T4 rectal adenocarcinoma. Patients received standard-dose radiation (50.4 Gy for 5.5 weeks) with concurrent infused 5-fluorouracil (5-FU) at 200 mg/m2 per day, 7 days per week. Oxaliplatin was given three times at 14-day intervals at 55, 70, or 85 mg/m2 during the 5.5-week radiation period, before resection. Adjuvant therapy consisted of four cycles of 5-FU (500 mg/m2 per week) with leucovorin (500 mg/m2 per week) given every 6 weeks. The main goals were to identify the maximum tolerated dose of oxaliplatin and the dose-limiting toxicities when given with 5-FU and RT. Secondary goals were to determine resectability, pathologic response, sphincter preservation, and overall survival rates. RESULTS: Twenty-one patients were enrolled, 5 at the 55 mg/m2 oxaliplatin dose level, 5 at 70 mg/m2, and 11 at 85 mg/m2. All patients were able to complete the preoperative chemoradiation regimen with no dose adjustments. No dose-limiting toxicities or differences in the type or extent of toxicity were noted among the groups. Nineteen patients underwent surgery (three abdominopelvic resections and 16 low anterior resections), for an 84% sphincter preservation rate. The pathologic complete response rate was 26% (5 patients), and minimal microscopic residual tumor was found in 21% (4 additional patients). CONCLUSIONS: Oxaliplatin was well tolerated at 85 mg/m2 given every 2 weeks in combination with standard preoperative chemoradiation for rectal cancer. The rates of major pathologic response and sphincter preservation are promising. 相似文献
20.
Sudo K Yamaguchi T Ishihara T Nakamura K Shirai Y Nakagawa A Kawakami H Uno T Ito H Saisho H 《International journal of radiation oncology, biology, physics》2007,67(1):219-224
PURPOSE: The primary objective of this study was to determine the maximum-tolerated dose (MTD) of S-1, an oral fluoropyrimidine derivative, with concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer. METHODS AND MATERIALS: Patients with histopathologically proven, unresectable, locally advanced pancreatic cancer were eligible. Radiotherapy was delivered in 1.8 Gy daily fractions to a total dose of 50.4 Gy over 5.5 weeks. S-1 was administered orally twice a day from Day 1 to 14 and 22 to 35 at escalating doses from 60 to 80 mg/m(2)/day. RESULTS: Sixteen patients were enrolled in this study. Three patients received S-1 at 60 mg/m(2)/day, 3 at 70 mg/m(2)/day, and 10 at 80 mg/m(2)/day. Though 1 patient at the final dose level (80 mg/m(2)/day) experienced a dose limiting toxicity (biliary infection with Grade 3 neutropenia), the MTD was not reached in this study. The most common toxicities were anorexia and leukocytopenia, with Grade 3 toxicity occurring in 31% and 6.3% of the patients, respectively. CONCLUSIONS: The recommended dose of S-1 with concurrent radiotherapy was determined to be 80 mg/m(2)/day from Day 1 to 14 and 22 to 35 in patients with locally advanced pancreatic cancer. Oral S-1 and radiotherapy is well tolerated and feasible and should be further investigated. 相似文献