Dose Of Paclitaxel In Patients Research Articles

Comparison of subsequent infusion hypersensitivity reactions to paclitaxel using two different infusion strategies.

The purpose of this study was to compare the incidence of rescue medication utilization with up to 3 subsequent doses of paclitaxel in patients who underwent an infusion rate escalation versus those who continued on the standard infusion rate after experiencing an initial paclitaxel infusion hypersensitivity reaction (HSR) requiring rescue medications. A retrospective, single-center review was conducted on patients who experienced a paclitaxel infusion HSR requiring rescue medications to their first or second lifetime dose of paclitaxel. A total of 99 patients were included for analysis, and from this group, 22 patients were continued on the standard infusion rate, while 77 patients were changed to an infusion rate escalation. The rate of subsequent rescue medication utilization was 5% in patients who were continued at the standard infusion rate versus 23% in patients who were changed to an infusion rate escalation (p = 0.064). The incidence of subsequent rescue medication utilization was unrelated to disease stage (p = 0.39), the paclitaxel dosing regimen (p = 0.99), or a diagnosis of asthma (p = 0.99). This single-center, retrospective study suggests that while not statistically significant, there was a potentially clinically meaningful increase in the rate of subsequent rescue medication utilization in patients who were changed to an infusion rate escalation compared to those who continued on the same standard infusion rate after experiencing an initial HSR to paclitaxel.

Outcomes of treatment with paclitaxel-coated devices for peripheral arterial disease

ObjectiveThe treatment of femoropopliteal peripheral artery disease (PAD) using paclitaxel-coated devices (PCDs) has been shown to improve patency in several randomized trials. However, a recent meta-analysis of trial data suggested an increased risk of mortality with PCD usage. Although subsequent studies have found no association with mortality, the subject has remained controversial. Thus, the aim of the present study was to further investigate the outcomes and causes of mortality for patients treated with PCDs. MethodsPatients who had undergone endovascular interventions for PAD from 2013 to 2016 at a single institution were reviewed. The patients were stratified by the use of PCDs, which included drug-coated balloons and drug-eluting stents. The cumulative dose of paclitaxel was calculated for the patients who had received multiple interventions. The causes of mortality were identified and compared between the two groups. ResultsOf the 366 included patients, 138 (38%) had received a PCD and 228 (62%) had received a non–drug-coated (NDC) device. Patients treated with PCDs were less likely to have undergone open surgery compared with patients treated with NDC devices. No differences were found in the indications or 30-day outcomes between the two groups. After a mean follow-up of 3.1 ± 1.8 years, no differences were found in the primary patency, reintervention rate, mean number of reinterventions, major amputation (5% vs 4%; P = .465), or mortality (16% vs 20%; P = .363) between the PCD and NDC groups. Also, no overall difference was found in the cause of mortality with and without PCD use or in the Kaplan-Meier survival curves. Furthermore, PCD use was not associated with an increased risk of mortality in Cox regression analysis. The cumulative dose of paclitaxel in patients treated with PCDs ranged from 383 to 49,259 μg (median, 7561 μg). A comparison of the patients treated with a cumulative dose of paclitaxel in the upper 50th percentile compared with the lower 50th percentile showed no significant differences in mortality (13% vs 19%; P = .333). ConclusionsPCD use was shown to be safe and not associated with an increased risk of long-term mortality in the present study. Continued monitoring of PCD use is warranted to ensure the safety of this technology.

Outcomes of Treatment With Paclitaxel-Coated Devices for Peripheral Arterial Disease

Treatment of femoropopliteal peripheral artery disease using paclitaxel-coated devices (PCD) has been shown to improve patency in several randomized trials. However, a recent meta-analysis of trial data suggested an increased risk of mortality with the use of this technology. Although subsequent studies have found no association with mortality, real-world data are lacking. Thus, the aim of this study is to investigate real-world outcomes and causes of mortality of patients treated with PCD. Patients who underwent endovascular interventions for peripheral artery disease from 2013 to 2016 at a single institution were reviewed. Patients were stratified based on the use of PCD. The cumulative dose of paclitaxel over a 3-year period was calculated among patients who received multiple interventions. Causes of mortality were identified and compared between the two groups. There were 138 (37.7%) patients who received an endovascular intervention with a PCD and 228 (62.3%) who received an endovascular intervention without paclitaxel. Patients treated with PCD were less likely to have prior open surgery compared to patients treated without paclitaxel. There were no differences in indication, TransAtlantic Inter-Society Consensus classification, or 30-day outcomes between the two groups. After 3-year follow-up, there was no difference in primary patency, reintervention rate, mean number of reinterventions, amputation (5.1% vs 3.5%; P = .465), or mortality (15.9% vs 19.7%; P = .363) between the PCD and non-PCD groups (Table). There was also no overall difference in the causes of mortality with and without PCD use or in the Kaplan-Meier survival curves (Figure). Furthermore, the use of PCD was not associated with an increased risk of mortality in Cox regression analysis. The cumulative dose of paclitaxel in patients treated with PCD ranged from 383 to 49,259 μg with a median dose of 7561 μg. Comparison of patients treated with cumulative doses of paclitaxel in the upper 50th percentile compared to the lower 50th percentile showed no significant difference in mortality (13.0% vs 19.1%; P = .333). PCD use is safe and not associated with an increased risk of long-term mortality in this study. However, PCD use was not associated with improved LER outcomes. Continued monitoring of PCD is warranted to ensure safety and efficacy of this new technology in a real-world setting.TableDemographics, comorbidities, procedural characteristics, and outcomesNon-PCD paclitaxelPCDP valueDemographics and comorbidities No. of patients228138 Age (years)69.7 ± 11.469.7 ± 11.6.866 Male sex148 (64.9)89 (64.5).935 Race.693White171 (77.0)102 (77.7)African American33 (14.9)16 (12.2)Other18 (8.1)13 (9.9) Body mass index27.5 ± 5.929.2 ± 6.4.015 Diabetes120 (52.6)73 (52.9).960 Hypertension205 (89.9)133 (96.4).024 Coronary artery disease133 (58.3)75 (54.4).456 Chronic renal insufficiency31 (13.7)26 (18.8).192 Smoking.250Nonsmoker37 (16.4)30 (21.7)Former116 (51.3)73 (52.9)Current73 (32.3)35 (25.4) Prior endovascular revascularization53 (23.4)31 (22.5).846 Prior open revascularization30 (13.2)8 (5.8).025 Preoperative ABI0.7 ± 0.30.8 ± 0.3.290 Indication.195Asymptomatic5 (2.2)1 (0.7)Claudication131 (57.5)91 (65.9)Chronic limb-threatening ischemia92 (40.4)46 (33.3)Medications Antiplatelet192 (84.2)109 (79.0).205 Statin161 (70.6)99 (71.7).818Procedure characteristics TASC classification.227TASC A24 (26.1)22 (23.4)TASC B29 (31.5)22 (23.4)TASC C12 (13.0)9 (9.6)TASC D27 (29.4)41 (43.6)30-Day outcomes Return to operating room16 (7.3)9 (6.8).872 Any complication34 (14.9)17 (12.3).487 Mortality4 (1.75)0 (0.0).1183-Year outcomes Primary patency73 (52.4)45 (42.9).150 Ipsilateral reintervention67 (29.4)53 (38.4).075 Ipsilateral major amputation8 (3.5)7 (5.1).465 All-cause mortality45 (19.7)22 (15.9).363Deaths.807 No. of patients4522 Cause of deathCardiovascular12 (26.7)9 (40.9)Cancer5 (11.1)1 (4.5)Respiratory2 (4.4)2 (9.1)Neurologic1 (2.2)0 (0.0)Gastrointestinal2 (4.4)1 (4.6)Renal0 (0.0)0 (0.0)Infectious8 (17.8)3 (13.6)Other/unspecified15 (33.3)6 (27.3)ABI, Ankle-brachial index; PCS, paclitaxel-coated device; TASC II, Inter-Society Consensus of the Management of Peripheral Artery Disease.Values are mean ± standard deviation or number (%), unless otherwise indicated. Open table in a new tab

Comparison of standard versus high dose of paclitaxel with ifosfamide and cisplatin (TIP) in salvage therapy of germ cell tumors (GCTs).

e15028 Background: Currently, TIP with higher dose of paclitaxel (250mg/m2) is considered standard salvage chemotherapy in GCTs with good prognostic features. However, until 2007, we utilized regimen with standard dose of paclitaxel (175mg/m2). The aim of this study was to compare the efficacy of TIP with the standard versus higher dose of paclitaxel as first salvage therapy for patients with relapsed GCTs. Methods: This retrospective study included 64 patients with relapsed GCTs treated with TIP as first salvage therapy between 1998 and 2010 in two major cancer centers in Slovakia. Forty five patients (70%) patients had favorable prognostic features for response (testis primary tumor site and prior complete response to induction chemotherapy regimen). Four cycles of standard dose (175mg/m2, 37 patients) or higher dose (250 mg/m2, 27 patients) of paclitaxel (day 1) with ifosfamide 1.2 g/m2 (day 1-5) and cisplatin 20 mg/m2 (day 1-5) were given 21 days apart with G-CSF support, followed by resection of resectable radiographic residua. Results: Nineteen of 37 (51%) patients treated with standard dose of paclitaxel achieved favourable response (complete remission or partial remission with negative serum tumor markers) compared to 20 of 27 (74%) patients treated with higher dose of paclitaxel (p = 0.07). In median follow-up of 23.9 months 37 patients (58%) experienced disease relapse and 33 (52%) patients died. Patients treated with higher dose of paclitaxel had better progression-free survival (median: not reached vs. 7 months, HR = 0.54, 0.28 - 1.04; p = 0.06) and overall survival (median: not reached vs. 33 months, HR = 0.69, 0.34-1.39; p = 0.31) compared to patients treated with standard dose of paclitaxel. Conclusions: Our data support the hypothesis that higher dose of paclitaxel with ifosfamide and cisplatin is associated with better outcome compared to standard dose of paclitaxel in patients with relapsed GCTs treated in first relapse.

Pharmacokinetic study of weekly administration dose of paclitaxel in patients with advanced or recurrent gastric cancer in Japan

We aimed to clarify the relationship between the maximum tolerated dose and plasma concentration of paclitaxel in Japanese patients with gastric cancer on a weekly paclitaxel administration regimen. Thirty-three patients with advanced or recurrent gastric cancer were treated with escalating doses of paclitaxel, administered weekly, along with a fixed dose of 5-fluorouracil or cisplatin. The plasma concentration of paclitaxel remained above 8.5 ng/ml for 24 h after administration. The mean area under the curve increased significantly with escalating dosage levels (R = 0.63; P 0.001). At level 4, patients showing dose-limiting toxicity had a significantly higher plasma paclitaxel concentration than patients without it. The weekly administration of paclitaxel, for which a single dose is about one-third of the dose for a tri-weekly treatment regimen, is clinically feasible and appropriate in terms of toxicity and the maintenance of an effective plasma concentration.

Phase I study of a weekly schedule of a fixed dose of cisplatin and escalating doses of paclitaxel in patients with advanced oesophageal cancer

The objective of this study was to determine the toxicities and maximum tolerated dose (MTD) of a dose-dense schedule with a fixed dose of cisplatin and escalating doses of paclitaxel in patients with metastatic or irresectable squamous cell-, adeno-, or undifferentiated carcinoma of the oesophagus. Patients received paclitaxel over 3 h followed by a 3-h infusion of a fixed dose of cisplatin of 70 mg/m 2 on days 1, 8, 15, 29, 36 and 43. The starting dose of paclitaxel was 80 mg/m 2. Patients were re-treated if white blood cell count (WBC) was ⩾1×10 9 cells/l, except for day 29 when the WBC had to be ⩾3×10 9 cells/l. Six patients were treated at each dose level. The dose of paclitaxel was increased by 10 mg/m 2 per level. Of the 24 patients enrolled, 13 had adenocarcinoma, 10 had squamous cell carcinoma and one had an undifferentiated carcinoma. All patients were evaluable for toxicity and 22 of 24 patients were evaluable for response. The paclitaxel dose could be escalated to 110 mg/m 2. At this dose, 3 out of 6 patients developed dose-limiting toxicity (DLT) including neutropenic enterocolitis with sepsis, vomiting and diarrhoea. Diarrhoea grades 3 and 4 was seen in 4 (17%) patients. Two of these patients died of neutropenic enterocolitis. Neutropenia grades 3 or 4 was seen in 20 (83%) patients, but apart from the two patients with neutropenic enterocolitis no other infectious complications were seen. Mild to moderate sensory neurotoxicity was seen in 11 (46%) patients (grade 1 in 8 patients and grade 2 in 3 patients). Other toxicities were mild and easily manageable. Of the 22 evaluable patients, 11 (50%) patients achieved a partial or complete response with a median duration of 13 months. Ten patients with either locally advanced disease or supraclavicular or celiac lymph nodes received additional local treatment after response to chemotherapy, seven patients are still without evidence of disease after a median follow-up of 32 months. Paclitaxel at a dose 100 mg/m 2 infused over 3 h followed by a 3-h infusion of 70 mg/m 2 cisplatin can be recommended for further studies in patients with metastatic or unresectable oesophageal cancer. Occurring diarrhoea should be handled with caution because it may be a sign of neutropenic enterocolitis. The response rate of this dose-dense schedule seems encouraging.

Long-term results and pharmacokinetics of high-dose paclitaxel in patients with refractory epithelial ovarian carcinoma.

The purpose of this study was to analyze the efficacy and toxicity of a high dose of paclitaxel in patients with ovarian cancer refractory to platinum chemotherapy. Another phase II study of hydroxyurea was run in the same patient population. Fifty patients with measurable ovarian cancer were entered on this phase II study at The University of Texas M. D. Anderson Cancer Center. Treatment consisted of 250 mg/m2 of paclitaxel given by continuous intravenous infusion over 24 h every 3 weeks. Patients with disease unresponsive to paclitaxel could then be crossed over to hydroxyurea, and vice versa. Twenty-five (53%) out of 47 evaluable patients had a response (two complete responses and 23 partial responses). Twelve (26%) patients had stable disease. The median survival was 11.3 months. The main toxic effect was neutropenia (98% of patients) with 28 (9%) episodes of neutropenic fever. Neutropenia required therapy with granulocyte colony-stimulating factor. Other side effects were alopecia (100%), anemia (98%), gastrointestinal problems (57%), stomatitis (27%), and neurotoxicity (55%). Paclitaxel administered at a high dose as a single agent proved to be very active in patients who had platinum-refractory ovarian cancer and was well tolerated. Further studies of high-dose paclitaxel in patients with ovarian carcinoma are indicated.

Multicenter, randomized comparative study of two doses of paclitaxel in patients with metastatic breast cancer.

The objective of this multicenter study was to compare the therapeutic index of two different doses of paclitaxel given as a 3-hour infusion in patients with metastatic breast cancer (MBC), who had failed to respond to previous chemotherapy. A total of 471 patients with MBC were randomized to receive intravenous paclitaxel at a dose of 175 or 135 mg/m2 every 3 weeks. Better treatment results were achieved with high-dose (HD) versus low-dose (LD) paclitaxel: overall response rate, 29% versus 22% (P = .108); complete response (CR) rate, 5% versus 2% (P = .088); median time to disease progression, 4.2 versus 3.0 months (P = .027); and median survival time, 11.7 versus 10.5 months (P = .321). Patients previously exposed or resistant to anthracyclines were as likely to respond as those without such prior exposure. Treatment was well tolerated, as documented by the number of administered treatment courses (median, six v five; range, one 17 v one to 18), the low frequency of dose reductions (14% v 7%, P = .024), and the small number of patients (n = 9 or 4% vn = 5 or 2%) who required treatment discontinuation for adverse reactions. The incidence and severity of neutropenia and peripheral neuropathy were dose-related. After quality-of-life-adjusted time-to-progression analysis, the HD arm (175 mg/m2) retained its advantage over the LD arm (135 mg/m2). The results of this trial substantiate the activity of paclitaxel in the treatment of MBC. The observed superior efficacy with a dose of 175 mg/m2 over 135 mg/m2 suggests a dose-effect relationship. The clinical activity in anthracycline-resistant patients is particularly noteworthy. Paclitaxel in breast cancer needs further evaluation in large trials that use combination chemotherapy and involve earlier disease stages.