Efficacy of weekly administration of paclitaxel for advanced or recurrent gastric cancer with peritoneal dissemination

We report 3 gastric cancer patients with peritoneal dissemination who failed to take TS-1 due to adverse effects and who were successfully treated with weekly paclitaxel administered intravenously. The patients were 2 men and 1 woman from 73 to 82 years in age. The histological types of gastric cancer were undifferentiated adenocarcinoma in all cases. Intravenous infusion of TXL (62-80 mg/m2) after short premedication was continued for 3 weeks followed by 1 week rest. Clinical symptoms, including ascites and intestinal obstruction, improved only after administration of 1 cycle in all patients. Except for 1 event with grade 3 neutropenia, no major adverse reactions were observed. Weekly administration of paclitaxel may be a promising chemotherapy for controlling peritoneal metastasis and improving the quality of life of patients with advanced or recurrent gastric cancer.     

Phase I trial of carboplatin and weekly paclitaxel in patients with advanced non-small-cell lung cancer

OBJECTIVE: This study was designed to determine the maximum tolerated dose of paclitaxel administered weekly in combination with carboplatin and to assess its dose limiting toxicity and preliminary activity in patients with previously untreated, advanced non-small-cell lung cancer. METHODS: Carboplatin was administered at a fixed dose that maintained an area under the curve of 6. Paclitaxel was given over 1 h once a week for 3 weeks starting at 60 mg/m(2) and escalated in 10 mg/m(2) increments. RESULTS: Twenty-one patients were treated with six dose levels (60, 70, 80, 90, 100, 110 mg/m(2)) of paclitaxel. The dose limiting toxicity was infection and the maximum tolerated dose was 110 mg/m(2). Nine of 21 (42.9%) patients demonstrated a therapeutic response. CONCLUSION: Weekly paclitaxel and carboplatin were well tolerated. Based on our results, 100 mg/m(2) of paclitaxel for 3 weeks of a 4-week cycle, in combination with carboplatin, was recommended for a phase II study.     

Phase I study of carboplatin, doxorubicin and weekly paclitaxel in patients with advanced ovarian carcinoma.

BACKGROUND: Doxorubicin is an active compound in epithelial ovarian cancer (EOC), but adding it to carboplatin-paclitaxel causes toxicity. Toxicity can be reduced by weekly administration. We examined the tolerability of weekly paclitaxel in combination with carboplatin and doxorubicin. PATIENTS AND METHODS: Chemotherapy na?ve patients with EOC were treated with doxorubicin (50 mg/m(2) day 1), carboplatin (AUC 6 day 1) and paclitaxel (days 1, 8, 15, 21), 28-day cycle. Three patients were treated at each paclitaxel dose level, starting at 60, 75 and 90 mg/m(2)/week. If more than two patients in a cohort experienced dose-limiting toxicity (DLT) three more patients were treated at the dose level below. RESULTS: Twelve patients with advanced EOC received a median of six cycles (range 2-6) of the three-drug combination. DLT occurred at dose level 3: prolonged grade 4 febrile neutropenia, 1 patient; grade 3 peripheral neuropathy, 1 patient. All six patients treated at dose level 2 experienced short-lived grade 4 neutropenia, which led to dose modifications resulting in an actual delivered dose of paclitaxel of 64 mg/m(2)/week. Eight out of 12 patients had measurable disease on CT scan: four obtained a partial remission; three had stable disease. CONCLUSIONS: The combination of carboplatin, doxorubicin and paclitaxel in patients with EOC is active and its main toxicity is myelosuppression. Dose intensity of paclitaxel can be maintained in a three-drug combination through weekly administration (65 mg/m(2)).     

Randomized phase II trial of weekly paclitaxel combined with carboplatin versus standard paclitaxel combined with carboplatin for elderly patients with advanced non-small-cell lung cancer

BackgroundThe optimal platinum doublet regimen in elderly patients with non-small-cell lung cancer (NSCLC) is still uncertain. We conducted a randomized phase II study to compare the efficacy and safety of weekly paclitaxel combined with carboplatin with those of the standard schedule.Patients and methodsElderly patients (age ≥70 years) with advanced NSCLC were randomly assigned to either the weekly arm {70 mg/m² paclitaxel on days 1, 8, and 15 and carboplatin [area under the curve (AUC) = 6] on day 1} or the standard arm [200 mg/m² paclitaxel and carboplatin (AUC = 6) on day 1]. The primary end point was the overall response rate (ORR).ResultsEighty-two patients were enrolled. The ORR and median progression-free survival were 55% and 6.0 months for the weekly arm and 53% and 5.6 months for the standard arm. Grade 3/4 neutropenia and peripheral neuropathy were observed in 41% and 0% of the patients in the weekly arm and in 88% and 25% in the standard arm, respectively.ConclusionsThis is the first randomized study that compares the platinum doublet designed specifically for the elderly. Regarding the safety, the weekly regimen was less toxic than the standard regimen and seems to be preferable for elderly patients with advanced NSCLC.     

单周方案紫杉醇单药治疗在晚期胃癌应用的进展

晚期胃癌给予化疗加支持治疗，患者的生存率和生活质量都较单独给予支持治疗高。目前，在晚期胃癌治疗中，紫杉醇类的药物是最有前途的细胞毒药物之一。紫杉醇的单药使用，特别是低剂量每周的单药治疗，显示出了令人振奋的作用，且毒副反应较低，起效快，迅速缓解症状，对于一些老年、生存状况差、不适于进行联合化疗，甚至失去常规化疗指征的晚期胃癌患者，不失为一种可供选择的治疗方法。本文着重介绍小剂量每周紫杉醇单药治疗晚期胃癌的一些临床报道。     

Phase 1 study of veliparib with carboplatin and weekly paclitaxel in Japanese patients with newly diagnosed ovarian cancer

This phase 1, open‐label, dose‐escalation study was conducted to determine the safety, tolerability, pharmacokinetics and preliminary efficacy of veliparib with carboplatin and weekly paclitaxel in Japanese women with newly diagnosed, advanced ovarian cancer. Patients received veliparib at 100 or 150 mg b.i.d. on days 1–21 with carboplatin (area under the concentration–time curve 6 mg/mL?min) on day 1 and paclitaxel 80 mg/m² on days 1, 8 and 15 every 3 weeks for up to 6 21‐day cycles. Dose escalation followed a 3 + 3 design to determine dose‐limiting toxicities, maximum tolerated dose and the recommended phase 2 dose. Nine patients (median age 62 [range 27–72] years) received a median of 5 (range 3–6) cycles of treatment (3 at 100 mg, 6 at 150 mg). There were no dose‐limiting toxicities. The most common adverse events of any grade were neutropenia (100%), alopecia (89%), peripheral sensory neuropathy (78%), and anemia, nausea and malaise (67% each). Grade 3 or 4 adverse events were associated with myelosuppression. Pharmacokinetics of carboplatin/paclitaxel were similar at both veliparib doses. Response, assessed in five patients, was partial in four and complete in one (objective response rate 100%). The response could not be assessed in four patients who had no measurable disease at baseline. The recommended phase 2 dose of veliparib, when combined with carboplatin/paclitaxel, is 150 mg b.i.d. Findings from this phase 1 trial demonstrate the tolerability and safety of veliparib with carboplatin/paclitaxel, a regimen with potential clinical benefit in Japanese women with ovarian cancer.     

A case of effective weekly paclitaxel administration for advanced gastric cancer

A 74-year-old man was admitted to our hospital with severe anemia. Endoscopic examination revealed a type 3 advanced gastric cancer. Abdominal computed tomography revealed massive lymph node metastasis(N3). We performed distal gastrectomy(noncurative resection)because anemia had progressed. After operation, we administered S-1/CDDP combination chemotherapy. Although he received two courses of S-1/CDDP, renal dysfunction was found. Afterwards a rise in tumor marker(CEA)occurred, so we changed to chemotherapy with weekly paclitaxel. Abdominal computed tomography then revealed a complete response(CR)after the chemotherapy was completed. At present, 7 years after the operation, the patient remains free of a rise in tumor markers and presents no evidence of a recurrence.     

Comparison of outcomes for elderly patients treated with weekly paclitaxel in combination with carboplatin versus the standard 3-weekly paclitaxel and carboplatin for advanced nonsmall cell lung cancer

BACKGROUND: The purpose of this study was to compare the outcomes between elderly (aged > or = 70 years) patients treated with paclitaxel on a weekly basis and with carboplatin (every 4 weeks) versus the standard 3-weekly regimen of carboplatin and paclitaxel for first-line therapy of advanced nonsmall cell lung cancer. METHODS: Of the 444 patients enrolled, 136 (31%) were aged > or = 70 years. Seventy-two patients were randomized to the weekly schedule (paclitaxel, 100 mg/m(2) weekly for 3 of 4 weeks; carboplatin, area under the curve [AUC] = 6 mg/mL.min on Day 1 every 4 weeks), and 64 patients were randomized to the standard schedule (paclitaxel, 225 mg/m(2); carboplatin, AUC = 6 mg/mL.min on Day 1 every 21 days). Patients with stable disease or objective response after 4 cycles of therapy were eligible for maintenance therapy with weekly paclitaxel (70 mg/m(2), 3 of 4 weeks). RESULTS: The response rate for elderly patients was 26% on the weekly regimen and 19% on the standard schedule. The median survival duration for the weekly and the standard schedules was 37 weeks and 31 weeks, respectively. The 1-year survival rates were similar at 31% and 33%. Grade 3 to 4 anemia was more common on the weekly schedule (16% vs 6%), whereas grade 3 neuropathy was less common (5.5% vs 9.5%). Nausea and emesis were also less frequent on the weekly schedule. CONCLUSIONS: Efficacy was similar between the weekly regimen and the standard regimen of carboplatin and paclitaxel for elderly patients with advanced NSCLC and may be advantageous based on its favorable tolerability profile.     

Efficacy of weekly paclitaxel in patients with advanced gastric cancer refractory to docetaxel-based chemotherapy

Background

Only partial cross-resistance between docetaxel and paclitaxel has been demonstrated in breast and ovarian cancers. Whether weekly paclitaxel is effective in patients with advanced gastric cancer refractory to docetaxel-based chemotherapy remains unclear, and we aimed to clarify the efficacy and safety of weekly paclitaxel in such patients.

Methods

Patients who had received docetaxel-based regimens were assigned to the prior-docetaxel group, and those who had never received docetaxel were designated as the non-docetaxel group. Paclitaxel at 80?mg/m² was administered by intravenous infusion in all patients, and this was repeated weekly for 3?weeks out of 4.

Results

Between April 2006 and June 2011, 65 patients were studied: 26 in the prior-docetaxel group and 39 patients were non-docetaxel group. The median age, gender, performance status, histological type, history of gastrectomy, and the locations and numbers of metastatic sites did not differ significantly between the two groups. In the prior-docetaxel group, the response rate (RR) was 14.2% (3/21) among patients with measurable lesions, median progression-free survival (PFS) was 79?days [95% confidence interval (CI), 47–135?days], and overall survival (OS) was 123?days (95% CI, 90–215?days) from the initiation of paclitaxel treatment. In the non-docetaxel group, the RR was 11.5% (3/26) among patients with measurable lesions, PFS was 82?days (95% CI, 52–106?days), and OS was 143?days (95% CI, 121–178?days). The efficacy of weekly paclitaxel thus appeared to be similar in the two groups.

Conclusions

Weekly paclitaxel was modestly active in patients with gastric cancer refractory to docetaxel-based chemotherapy.     

Efficacy and safety of the paclitaxel and carboplatin combination in patients with previously treated advanced ovarian carcinoma

Background: Platinum compounds are the most active drugs in ovarian cancer treatment; cisplatin and carboplatin demonstrated similar efficacies but different toxicity profiles. Paclitaxel combined with cisplatin as first-line treatment improved overall survival when compared to a cisplatin-cyclophosphamide combination, but generated higher rates of neutropenia, febrile neutropenia and neurotoxicity. The paclitaxel-carboplatin combination may be better tolerated than cisplatin–paclitaxel.Design: The objective of the present study was to assess the efficacy and safety of the combination of paclitaxel and carboplatin in previously treated advanced ovarian cancer patients.Patients and methods: During or after platinum-based chemotherapy, 73 patients with progressive advanced epithelial ovarian carcinoma were enrolled to receive every four weeks a three-hour infusion of paclitaxel 175 mg/m² followed by a 30-minute carboplatin infusion. The carboplatin dose was calculated to obtain the recommended area concentration-versus-time under the curve of 5 mg·ml^-1·min.Results: Toxicity and response could be evaluated for 72 and 62 patients, respectively. Eleven complete and 15 partial responses gave an overall response rate of 42% (95% CI: 30%–54%). Response rates for platinum-refractory patients and those with early (3 and <12 months) and late (>12 months) relapses were 24%, 33% and 70%, respectively. The respective median response duration, the median progression-free survival and median overall survival were 8, 6 and 14 months. Myelosuppression was the most frequent and severe toxicity. Grade 3 and 4 neutropenia occurred, respectively in 30% and 23% of the cycles; 6% of the cycles benefited from medullary growth factors. Only one episode of febrile neutropenia was observed. Grade 3 and 4 thrombocytopenia occurred, respectively during 3% and 1% of the cycles. Alopecia was frequent. Transient peripheral neuropathy developed in 47% of patients but was severe in only one patient. One early death was attributed to progressive disease and possibly to therapy.Conclusion: This combined paclitaxel–carboplatin therapy is effective and can be safely administered to ovarian cancer patients who relapse after one or two regimens of platinum-based chemotherapy.     

A phase II study of weekly paclitaxel combined with carboplatin for elderly patients with advanced non-small cell lung cancer

We conducted this phase II study to explore the efficacy and safety of weekly paclitaxel combined with carboplatin in elderly patients with advanced non-small cell lung cancer (NSCLC). Elderly patients (> or = 70 years old) of stage IIIB, IV, or recurrent NSCLC with PS 0 or 1 were enrolled. Patients received paclitaxel at a dose of 70 mg/m2 on Days 1, 8, 15, and carboplatin at the target dose of the area under the curve (AUC) of six on Day 1 every 28 days for at least two cycles. Forty-two patients were enrolled and 40 patients were treated with a median of three cycles (range, 1-5). The overall response rate (ORR) was 45% (95% confidence interval, 30-60%). The median survival time (MST) was 14 months and the 1-year survival rate was 62%. Twenty-eight patients (70%) had grade 3/4 neutropenia and two patients (5%) experienced grade 3 febrile neutropenia. Non-hematological toxicities were generally mild to moderate and grade 3 peripheral neuropathy was seen in one patient (3%). There was one treatment-related death by infection due to neutropenia. Weekly paclitaxel and carboplatin combination chemotherapy was an effective and safe regimen in elderly patients with advanced NSCLC. A randomized trial comparing this treatment with the conventional tri-weekly regimen of paclitaxel and carboplatin is warranted.     

Compared medical costs of treating ovarian cancer patients with weekly paclitaxel, carboplatin (TC) chemotherapy

In order to see how the medical costs will change when the DPC (Diagnosis Procedure Combination) is implemented, the team calculated possible fees on DPC for patients who received weekly TC chemotherapy between October and December 2004 at the university gynecology department, and compared them with fees calculated by the piece-rate system. The team also simulated the cost difference between inpatients and outpatients, on the assumption that the same patients received chemotherapy as outpatients. The study has found that the hospital would pay 114,098 points worth of costs for the 18 patients (average age, 51.9), when the fees are requested on a DPC basis. It was also found that the fees for the same patients would be reduced by 53,617 points, if they were treated as outpatients. The study shows that, when the patients are physically fit for outpatient visits for weekly TJ chemotherapy, this approach, compared to an inpatient-basis, would be beneficial for both the hospital and patients.     

Treatment of patients with advanced lung cancer and poor performance status

Patients with advanced lung cancer and poor performance status (PS) have been underrepresented in clinical trials. As a consequence, the management of these patients in clinical practice is empirical and inconsistent. Recent data in advanced non-small-cell lung cancer (NSCLC) indicate that patients with a PS of 2 tend to benefit from first-line chemotherapy with respect to symptom improvement and perhaps overall survival. Whether single-agent therapy or combination chemotherapy is preferable remains debatable. In previously treated patients with NSCLC, gefitinib produced a substantial rate of clinical benefit, and erlotinib led to an improvement in survival compared with placebo in studies that included a significant percentage of patients with poor PS. In patients with recurrent small-cell lung cancer, who frequently present with a compromised PS, the use of topotecan as a single agent led to an improvement in PS in approximately one third of these patients without excessive toxicities. Patients with advanced lung cancer and a PS of 2 have been the focus of intense clinical investigation in recent years. When more specific data for this special population become available, it will hopefully lead to more consistent management and improved outcomes.     

紫杉醇脂质体联合卡铂与紫杉醇联合卡铂治疗卵巢癌的疗效比较

目的探讨和比较紫杉醇脂质体联合卡铂与紫杉醇联合卡铂治疗卵巢癌的疗效。方法选取2012年5月至2015年5月间收治的60例卵巢癌患者,按照随机数字表法分为研究组和对照组,每组30例。研究组患者采用紫杉醇脂质体联合卡铂治疗,对照组患者采用紫杉醇联合卡铂治疗,比较两组的疗效及不良反应。结果研究组患者的总有效率为73.3%(22/30),对照组为70.0%(21/30),差异无统计学意义(P>0.05)。研究组患者的过敏反应、白细胞减少、血红蛋白减少、血小板减少、皮疹、肌痛、胃肠道反应发生率均显著低于对照组,差异有统计学意义(P<0.05),但两组患者的脱发发生率差异无统计学意义(P>0.05)。结论紫杉醇脂质体联合卡铂治疗卵巢癌与紫杉醇联合卡铂治疗卵巢癌疗效相当,但不良反应少。     

Phase II multicenter trial of a weekly paclitaxel and carboplatin regimen in patients with advanced breast cancer.

PURPOSE: To determine the activity of weekly paclitaxel plus carboplatin as first-line therapy in patients with advanced breast cancer (ABC) by assessing response rate, survival, and safety. PATIENTS AND METHODS: One hundred patients with ABC received paclitaxel 135 mg/m(2) (group 1, n = 20) and carboplatin area under the concentration-time curve (AUC) of 2. Paclitaxel was subsequently reduced to 100 mg/m(2) (group 2, n = 80) because of toxicity. The median age was 58.5 years, and most patients had an Eastern Cooperative Oncology Group performance status of 相似文献   

A phase II study of weekly paclitaxel and carboplatin in previously untreated patients with advanced non-small-cell lung cancer

Purpose: Both paclitaxel (P) and carboplatin (C) have a significant activity in non-small cell lung cancer (NSCLC). Weekly administration of P is active, is dose intense, and has a favorable toxicity profile. To evaluate the efficacy and toxicity of weekly P and C in advanced-stage NSCLC, we initiated this phase II study in patients with advanced NSCLC (III B with pleural effusion and stage IV). Patients and Methods: Eligible patients were treated with paclitaxel 100 mg/m² intravenously (iv) over 1 h followed by carboplatin AUC 2 iv over 30 min. This treatment was administered weekly for 3 of every 4 wk until disease progression or intolerable toxicities. Results: Of the 30 patients enrolled in the study, one patient did not meet the eligibility criteria. Of the remaining 29 patients, 6 did not complete at least two cycles of treatment and hence were not assessable for response. The overall response rate was 43.5% (10/23) (all partial responses). An additional 43.5% had stable disease. The median time to progression was 162 d and the median duration of response was 169 d. Overall survival at 1 yr on intent-to-treat analyses was 44% and median survival was 10.8 mo. We observed the following grade 3/4 toxicities: hypersensitivity to paclitaxel (13%), hypersensitivity to carboplatin (3%), neutropenia (31%), thrombocytopenia (7%); 31% experienced grade 1 neuropathy and 17% experienced grade 2 neuropathy. Conclusions: We conclude that weekly paclitaxel and carboplatin is active and very well tolerated in patients with advanced NSCLC.     

Usefulness of weekly administration of paclitaxel for advanced or recurrent gastric cancer

We report herein the efficacy and feasibility of weekly administration of paclitaxel for advanced/recurrent gastric cancer retrospectively. Eleven patients with advanced or recurrent gastric cancer who had received prior chemotherapy were treated with this regimen. Seventy mg of paclitaxel per m2 dissolved in 250 ml 5% glucose was administered by 1-hour intravenous infusion once a week for 3 weeks followed by 1 week rest. To avoid hypersensitivity reactions, the following short premedication was given to all the patients 1 hour before paclitaxel treatment: Dexamethasone 20 mg intravenously (i.v.), diphenhydramine 50 mg i.v., and ranitidine 50 mg i.v. Treatment cycle was 1 to 23 with an average cycle of 5.4. The response rate was 33% (2/6 with measurable lesions), the median time to progression was 104 days, and the median survival time was 160 days. Grade 3 neutropenia occurred in 27.2% of the patients. Weekly paclitaxel may be a promising regimen as a second-line chemotherapy for advanced/recurrent gastric cancer. However, special attention needs to be paid to the neutropenic adverse effect in gastric cancer patients with poor performance status than 2 (greater).     

Clinical study of weekly administration of paclitaxel for advanced and metastatic gastric cancer

Ten cases of advanced and metastatic gastric cancer treated by weekly administration of paclitaxel were studied. The patients were 50-72 years of age, including 9 men and 1 woman. In this study, paclitaxel was administered by 1 hour intravenous infusion at a dose of 50-80 mg/m2 every week. Administration was continued for 3 weeks with 1 week rest. One to four cycles were performed at minimum. Paclitaxel was administered in 5 cases as 1st line treatment, 4 cases as 2nd line treatment and 1 case as 3rd line treatment. There were 2 partial responders and no complete responders, and the overall response rate was 20%. The response rate was 100% in liver, 100% in lung, 16% in lymphnodes, and 0% in peritonial dissemination. The clinical symptoms of pain and jaundice abated in one case, the size of the tumor decreased in one case, and a temporary decrease of ascites due to peritonial dissemination was seen in two cases. The level of tumor marker was decreased in 3 out of 10 cases. Side effects included grade 3/4 leukopenia in 10% of patients, and alopecia in 50%, but peripheral neuropathy was not observed. Weekly administration of paclitaxel appears to be well-tolerated and effective against advanced and metastatic gastric cancer.     

A phase II evaluation of weekly paclitaxel plus carboplatin in advanced urothelial cancer

This Phase II trial was designed to evaluate the overall objective response rate, complete response rate, efficacy, and safety of weekly paclitaxel (Taxol) and carboplatin (Paraplatin) in the treatment of advanced urothelial carcinoma. Thirty-three patients with measurable, unresectable, stage III-IV carcinoma of the urothelium were enrolled. Paclitaxel (135 mg/m2) and carboplatin (AUC=2) were given by intravenous (IV) infusion weekly x 6 followed by two weeks rest. Patients were premedicated with oral dexamethasone, diphenhydramine, and cimetadine (or equivalent). Patient characteristics included an Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 (36%), one (36%), two (28%); median age 70 years (37-83); 29 (88%) male, four (12%) female; 16 (48%) patients had prior chemotherapy [eight postoperative (adjuvant), five neoadjuvant, three for metastatic disease] and eight (24%) had prior radiation therapy. Eight patients (24%) achieved objective responses, three complete responses (CR) and five partial responses (PR); one patient was not evaluable (patient died prior to first dose). The median duration of response was 13 months (range, 2-29). Nine patients (27%) had stable disease (SD) and 15 patients (45%) had progressive disease (PD). Median time to progression was 3.6 months (range, < 1-29) and median survival was 10.3 months (range, < 1-33). Grade 3 and 4 toxicities included: asthenia (46%), neutropenia (36%), leukopenia (15%), thromboembolism (12%), diarrhea (9%), nausea and vomiting (9%), hyperglycemia (7%), and neuropathy (6%). Two patients died of sepsis, one death was treatment-related. Weekly paclitaxel plus carboplatin shows promising activity; however in the current study, efficacy may have been limited by the toxicities associated with this dose-intensive regimen in an elderly, pretreated patient population with poor performance status. This regimen warrants further study, perhaps as a three out of four week regimen or at reduced doses.