Median Cumulative Dose Of Docetaxel Research Articles

Appropriate Number of Docetaxel Cycles in Castration-Resistant Prostate Cancer Patients Considering Peripheral Neuropathy and Oncological Control

Background: The number of cycles of docetaxel required for castration-resistant prostate cancer (CRPC) is unclear. This study estimated peripheral neuropathy (PN) incidence and the optimal number of treatment cycles in patients receiving docetaxel for CRPC. Patients and Methods: The study retrospectively reviewed 82 patients receiving docetaxel for CRPC at an institution between January 2005 and January 2017. Docetaxel (70 or 75 mg/m²) was administered every 3 weeks, and prednisone 5 mg or dexamethasone 0.5 mg was administered twice a day. Results: PN (grade ≥2) was noted in 32 (39.0%) patients. The median cumulative dose of docetaxel associated with PN was 675 mg/m². No factor significantly predicted the occurrence of PN. The prostate-specific antigen progression rate, prostate cancer-specific survival, and overall survival were significantly better with ≥8 cycles of docetaxel than with <8 cycles (p < 0.05). Conclusion: The incidence of PN is high, and 8 treatment cycles are optimal for patients receiving docetaxel for CRPC.

Phase I clinical study of cabazitaxel plus prednisolone for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in a Japanese population.

237 Background: Cabazitaxel (CBZ), a novel taxoid agent, promotes tubulin assembly and stabilizes microtubules, as docetaxel (DTX). CBZ had antitumor activity in DTX-resistant tumor models in vitro. We assessed dose-limiting toxicities (DLTs), safety and efficacy of CBZ in patients (pts) with mCRPC with prior DTX treatment. Methods: This was an open-label, dose escalation study of CBZ every 3 weeks, with daily prednisolone. Two CBZ dose levels (20 or 25 mg/m2) were set in the dose escalation cohort to determine the maximum tolerated dose (MTD). Pts in the expansion cohort received the MTD. DLTs were evaluated at cycle 1 and were defined as follows: Grade (Gr) 4 neutropenia &gt; 7 days, Gr 4 thrombocytopenia, Gr 4 febrile neutropenia (FN), or Gr 3/4 non-hematological toxicities. Gr 3/4 neutropenia was prospectively studied based on occurrence of Gr 3/4 neutropenia during prior DTX treatment. Results: A total of 48 pts received CBZ (median age 66.1 years; ECOG PS: 0, 34 pts; 1, 14 pts; median cumulative DTX dose 753 mg/m2). None of the evaluable pts in the dose escalation cohort experienced a DLT. All pts had at least one Gr 3/4 adverse event (AE). Frequent Gr 3/4 AEs at 25 mg/m2 were neutropenia (44 pts, 100%) and FN (24 pts, 54.5%). G-CSF prophylaxis was not allowed at cycle 1 and was only used in 10% of cycles from cycle 2 onward. Neutropenia occurrence during prior DTX treatment did not affect neutropenia or FN incidence during CBZ treatment. No pt discontinued CBZ due to neutropenia or FN and no toxic death was reported. In total, 12/41 pts (29.3%) had a PSA response, and 2/12 evaluable pts had a partial response as the best overall response. Conclusions: The safety profile of CBZ in Japanese pts was generally consistent with that reported in previous studies. The cumulative dose of prior DTX was higher and use of G-CSF prophylaxis less frequent than in previous studies, which may have contributed to the increased incidence of neutropenia and FN in Japanese pts. The majority of neutropenia and FN events were manageable and did not lead to treatment discontinuation. In terms of safety and efficacy, CBZ has a favourable risk–benefit profile in Japanese pts with mCRPC following prior DTX therapy. Clinical trial information: NCT01324583.

A lower dose of docetaxel at 60 mg/m2 could be continued longer for controlling peripheral edema in patients with metastatic breast cancer

Docetaxel is a key drug for metastatic breast cancer (MBC). In patients with MBC, the treatment objective is durable response with minimum toxicity. In Japan, the approved dose of docetaxel is 60-70mg/m(2) every 3weeks, whereas 75-100mg/m(2) docetaxel is common in the West. We retrospectively examined the prevalence of edema in patients with MBC who were treated with docetaxel. Seventy-seven patients received docetaxel at a dose of 60mg/m(2) every 3weeks with prophylactic premedication of dexamethasone, 8mg daily for 3days. Median follow-up time was 28months (range 4.3-98). Overall response was 25% (95% CI 15-34). Median time to progression and median survival time from the beginning of any systemic therapy for metastatic disease were 10 and 66months, respectively. Neutropenia was the most common toxicity, with grade 3-4 observed in 66%. Fifty-one percent of the patients experienced peripheral edema that could be controlled with oral diuretics. Grade 3 edema was observed in 4 patients only, and discontinuation because of edema was 9%. Other grade 3 or 4 toxicity was <5%. Median cumulative dose of docetaxel to onset of peripheral edema was 480mg/m(2) (range 60-780), and median cumulative given dose was 600mg/m(2) (range 84-2,928). These results suggest that treatment with docetaxel at 60mg/m(2) could be continued longer than the higher dose with manageable peripheral edema in patients with MBC. Further investigation is required to determine the superiority of low-dose docetaxel.

Predictors of toxicity of weekly docetaxel in chemotherapy-treated non-small cell lung cancers

Weekly docetaxel seems to be safe and effective compared with traditional tri-weekly docetaxel as a second-line treatment for non-small cell lung cancer. However, the risk factors for severe toxicity of weekly docetaxel in this group of patients are not well-described. Patients with advanced non-small cell lung cancer receiving weekly docetaxel as second- or third-line treatment at a medical center between 1999 and 2003 were identified from cancer registry and pharmacy records. The clinical characteristics, prior chemotherapy regimens, docetaxel administration schedules, and treatment efficacy were collected. Logistic regression was performed to identify risk factors for adverse outcomes and Cox's proportional hazards model was used to analyze cumulative-dose related adverse events. A total of 155 patients were analyzed for treatment effect and toxicity. The overall response rate of weekly docetaxel was 5.2% and the median survival was 8.1 months. The incidence of treatment withdrawal due to adverse events was 43.2% and was significantly related to previous anthracycline use (odds ratio, 4.582; p=0.0144) and chronic hepatitis B or C virus infection (odds ratio, 3.928; p=0.0058). The incidence of grade 3 or 4 neutropenia was 23.2% and was significantly associated with old age (odds ratio, 7.232; p<0.001), lower baseline white blood cell counts (odds ratio, 5.57; p<0.05), and chronic hepatitis B or C virus infection (odds ratio, 3.25; p<0.05). The incidence of fluid retention was 41.3% and the median cumulative dose of docetaxel at onset was 327 mg/m(2). Abnormal liver function status significantly increased the risk for fluid retention (odds ratio, 2.368; p<0.05); while pre-medication with steroids (odds ratio, 0.184; p<0.01), elevated albumin (odds ratio, 0.237; p<0.01), and previous surgical resection (odds ratio, 0.341; p<0.05) decreased the risk. Weekly docetaxel given as second- or third-line chemotherapy to patients with advanced non-small cell lung cancer harbors significant side effects. It should be given cautiously in elderly patients and in patients with chronic viral hepatitis or low white blood cell counts.

Prospective study of incidence and severity of epiphora and canalicular stenosis in patients with metastatic breast cancer receiving docetaxel.

To determine the incidence and severity of epiphora and canalicular stenosis in patients receiving docetaxel weekly or every 3 weeks. In this prospective trial, each patient underwent an ophthalmologic examination and probing and irrigation of the lacrimal drainage apparatus at baseline and every 4 to 6 weeks after initiation of docetaxel. During each visit, epiphora and canalicular stenosis were graded. Patients with epiphora were treated with tobramycin and dexamethasone drops. If epiphora worsened or if findings on probing and irrigation suggested further canalicular narrowing, silicone intubation was offered. Twenty-eight patients received docetaxel weekly, and 28 patients received docetaxel every 3 weeks. Eighteen patients (64%) who received weekly docetaxel developed epiphora. Epiphora was mild in seven patients, moderate in five, and severe in six. Nine patients had resolution of epiphora with tobramycin and dexamethasone administration. Nine patients had worsened canalicular stenosis; six underwent surgery. The median cumulative docetaxel dose was 496.5 mg at onset of epiphora and 889.5 mg at surgery. Eleven patients (39%) who received docetaxel every 3 weeks developed epiphora. The median cumulative docetaxel dose at onset of epiphora in this group was 420 mg. Epiphora was mild in nine patients, moderate in one, and severe in one. Nine patients had resolution of epiphora with tobramycin and dexamethasone administration. Two patients underwent surgery. Epiphora occurred in 64% of patients in the weekly group and in 39% of patients in the every-3-weeks group. Moderate or severe canalicular stenosis was seen in about one-third of patients in the weekly group and in none of the patients in the every-3-weeks group.

Prospective study of incidence and severity of epiphora and canalicular stenosis in patients with metastatic breast cancer receiving docetaxel

659 Background: To determine the incidence and severity of epiphora and canalicular stenosis in patients receiving weekly or every-3-weekly docetaxel. Methods: In this prospective trial, each patient underwent an ophthalmologic examination and probing and irrigation of the lacrimal drainage apparatus at baseline and at every 4–6 weeks after initiation of docetaxel. During each visit, epiphora and canalicular stenosis were graded. Patients with epiphora were treated with Tobradex drops. If epiphora worsened or findings on probing and irrigation suggested further canalicular narrowing, silicone intubation was offered. Results: 28 patients received weekly and 28 patients received every-3-weeks docetaxel. 18(64%) patients who received weekly docetaxel developed epiphora. Epiphora was mild in 7 patients, moderate in 5, and severe in 6. Nine patients had resolution of epiphora with Tobradex. Nine patients had worsened canalicular stenosis; 6 underwent surgery. The median cumulative docetaxel dose was 496.5 mg at onset of epiphora and 889.5 mg at surgery. 11 (39%) patients who received every-3-weeks docetaxel developed epiphora. The median cumulative docetaxel dose at the time of onset of epiphora in this group was 420 mg. Epiphora was mild in 9 patients, moderate in 1, and severe in 1. Nine patients had resolution of epiphora in response to Tobradex. Two patients underwent surgery. Conclusions: Epiphora occurred in 64% of patients in the weekly group and 39% of patients in the every-three-weeks group. Moderate or severe canalicular stenosis was seen in about one-third of patients in the weekly group and none of the patients in the every-3-weeks group. [Table: see text]

Predictors for toxicity profiles of weekly docetaxel in non-small cell lung cancers

17153 Background: Weekly docetaxel has been proved recently to be safer and equivalently effective compared with traditional tri-weekly docetaxel as second-line treatment for NSCLC. However, the risk factors for toxicity of weekly docetaxel in this group of patients are still unknown. Methods: We reviewed advanced NSCLC patients receiving 2nd line or 3rd line weekly docetaxel from 1999 to 2003 from cancer registry and pharmacy records in our hospital. Clinical characteristics, previous chemotherapy regimens, laboratory data, docetaxel administration schedules/dosage, and treatment efficacy were retrospectively collected. Logistic regression was performed to identify risk factors for adverse outcomes. Cox’s proportional hazards model was used to analyze cumulative-dose related adverse events. Results: A total 155 patients were analyzed for treatment effect and toxicity. The overall response rate of weekly docetaxel (36–40 mg/m2) was 5.16% and median survival of all patients was 8.1 months. The incidence of treatment withdrawal due to adverse events was 43.23 % and significantly related to previous anthracycline use (odds ratio 4.582; P = 0.0144) and chronic hepatitis B or C virus (HBV/HCV) infection(odds ratio 3.928; P=0.0058). The incidence of grade 3 or 4 neutropenia was 23.2% and was significantly associated with old age (odds ratio 7.232; P &lt; 0.001), lower baseline white count(odds ratio 5.57; P &lt; 0.05), and chronic HBV/HCV infection(odds ratio 3.25; P &lt; 0.05). The incidence of fluid retention was 41.29% and the median cumulative dose of docetaxel at onset was 327 mg/m2. Abnormal liver function significantly increased the risk for fluid retention(odds ratio 2.368; P &lt; 0.05); steroid premedication (odds ratio 0.184; P &lt; 0.01), higher albumin(odds ratio 0.237; P &lt; 0.01), and previous surgical resection(odds ratio 0.341; P &lt; 0.05) decreased the risk. Conclusions: Salvage weekly docetaxel for NSCLC patients in Taiwan remains toxic. Part of the reasons for the significant toxicities is that chronic HBV/HCV infection, which occurs in around 20% of general populations in Taiwan, represents a significant risk factor for neutropenia, fluid retention, and treatment withdrawal. The role of prophylactic anti-viral agents in these patients should be explored in the future. [Table: see text]

Phase II Study of Concurrent Administration of Doxorubicin and Docetaxel as First-Line Chemotherapy for Metastatic Breast Cancer

Objective: To evaluate the efficacy and toxicity of concurrent administration of doxorubicin and docetaxel, without prophylactic use of granulocyte colony-stimulating factor, as first-line chemotherapy in patients with metastatic breast cancer (MBC). Methods: This multi-institutional study enrolled 40 women; 37 were assessable for efficacy and all 40 patients were evaluated for toxicity. Treatment consisted of 50 mg/m² doxorubicin and 60 mg/m² docetaxel on day 1 every 3–4 weeks. Results: Patients received a total of 251 cycles of chemotherapy (median, 5 cycles; range, 1–13 cycles). Of the 37 patients assessable for efficacy, 2 had a complete response and 24 had partial responses, which accounted for a 70% objective response rate (95% confidence interval, 53–84%). The median time to treatment failure was 30.1 weeks (range, 3.3–80.7 weeks). Grade 4 neutropenia was observed in 88% of patients and was the most frequent haematological toxicity. Febrile neutropenia was seen in 40% of patients, but no severe infections were observed. Non-haematological toxicity was generally tolerable. There were 2 grade 4 adverse events, which included 1 bleeding duodenal ulcer and 1 hypersensitivity reaction, but grade 3 episodes were infrequent. None of the patients developed congestive heart failure or asymptomatic decrease of left ventricular ejection fraction to less than 50%. Fluid retention syndrome ≤ grade 2 was observed in 25% of patients at a median cumulative dose of docetaxel of 270 mg/m². Conclusion: Concurrent administration of 50 mg/m² doxorubicin and 60 mg/m² docetaxel is active with a manageable toxicity profile as first-line chemotherapy for MBC.

Corticosteroids significantly delay the onset of docetaxel-induced fluid retention: final results of a randomized study of the European Organization for Research and Treatment of Cancer Investigational Drug Branch for Breast Cancer.

To confirm the efficacy of docetaxel in patients with breast cancer previously treated with one chemotherapy regimen for advanced or metastatic disease and to compare the incidence of fluid retention (FR) and skin toxicity when docetaxel is administered with and without prophylactic corticosteroids. Eighty-three patients, pretreated with one chemotherapy regimen for metastatic breast cancer (MBC) with bidimensionally measurable and progressive disease, were eligible for this randomized trial. Docetaxel with prophylactic oral antihistamine was administered at a dose of 50 mg/m2 as a 1-hour infusion on days 1 and 8 every 21 days and patients were randomized to receive methylprednisolone (40 mg days -1, 0, 1, 7, 8, and 9 of each cycle) (arm A) or no methylprednisolone (arm B). Twenty-eight patients (34%, 95% confidence interval [CI], 23% to 45%) achieved on objective response. The median time to disease progression and median overall survival time were 5 and 13.5 months, respectively. In total, 415 cycles of docetaxel were administered (arm A: N = 219, median = six; arm B: N = 196, median = five). The most common toxicity observed was grade 3 or 4 neutropenia, which occurred in 79% of patients. Clinically significant nonhematologic side effects included skin reactions and asthenia. In an intent-to-treat analysis, patients who received methylprednisolone premedication had a delayed onset of FR (median time to onset of FR: arm A, 84 days; arm B, 62 days; P = .01) and received a higher median cumulative dose of docetaxel before the onset of FR (arm A, 333 mg/m2; arm B, 215 mg/m2; P = .001). There was no statistically significant difference in the incidence of skin toxicity between the two arms. Docetaxel, at this dose and schedule, has definite antitumor activity in pretreated MBC patients. Moreover, this is the first randomized trial to show that corticosteroids have a favorable impact on docetaxel-induced FR.

Docetaxel is a major cytotoxic drug for the treatment of advanced breast cancer: a phase II trial of the Clinical Screening Cooperative Group of the European Organization for Research and Treatment of Cancer.

This trial investigated the toxicity and efficacy of docetaxel as first-line chemotherapy in women with heavily pretreated advanced breast cancer. From April 1992 to August 1992, 35 patients with advanced breast cancer from 29 to 65 years of age with a performance status of 0 to 2 were entered onto the study. Docetaxel 100 mg/m2 was administered every 3 weeks as a 1-hour infusion on day 1 without routine premedication for hypersensitivity reactions. Thirty-one patients were assessable for response. Previous adjuvant chemotherapy had been given to 11 patients. Five complete responses (CRs) and 16 partial responses (PRs) were observed, for an overall response rate of 67.7% (95% confidence interval, 49% to 83%). A CR occurred at 13 of 45 assessable sites (four liver, two lung, three breast, three lymph node, and one skin). The median duration of response was 44+ weeks, the median time to disease progression 37+ weeks, and the median overall survival time 16+ months. Among 34 patients assessable for toxicity (177 cycles; median, five cycles per patient), the following side effects were reported: nadir neutropenia grade 3 (three patients); grade 4 (31 patients); no grade 3 to 4 infection, acute hypersensitivity-like reaction (10 patients); grade 2 to 3 alopecia (all patients); and grade 2 to 3 nausea and vomiting (six patients). Fluid retention occurred in 26 patients and consisted of weight gain, edema alone (15 patients), or edema associated with serous effusion (11 patients). This side effect led to treatment discontinuation in 16 of 21 responding patients after a median of five cycles and a median cumulative dose of docetaxel of 574 mg/m2. Our data suggest that docetaxel has major antitumor activity when used as a single cytotoxic agent as first-line chemotherapy in advanced breast cancer.