Phase II trial of utidelone as monotherapy or in combination with capecitabine in heavily pretreated metastatic breast cancer patients.

BACKGROUND: The treatment of metastatic breast cancer (MBC) remains a great clinical challenge as drug resistance frequently develops. Alternative agents that can overcome drug resistance would offer new therapeutic options. The primary aim of this phase II study was to evaluate the efficacy and safety of utidelone as a monotherapy or in combination with capecitabine in metastatic breast cancer patients previously treated with and resistant to anthracyclines and taxanes. METHODS: In two open-label, noncomparative clinical studies, patients with metastatic breast cancer who previously received anthracycline- and/or taxane-containing regimens were given (1) 25 to 35 mg/m(2)/day intravenously infused utidelone, once daily for 5 days, in combination with 14 days of 2000 mg/m(2) capecitabine, divided in two equal daily oral doses or (2) 40 mg/m(2)/day intravenously infused utidelone, once daily for 5 days. These regimens were administered per each 21-day treatment cycle, and the maximum of treatment cycles allowed per protocol is 6. Objective response rate (ORR), progression-free survival (PFS), and tolerability were evaluated. RESULTS: In the combination study, 33 patients completed a median of 6 cycles of therapy, which was the highest cycles a trial patient could receive under the criteria of the study protocol. Efficacy was evaluated (n = 32) with an ORR of 42.4 % (FAS, 95 % CI, 26.6, 60.9) and a median PFS of 7.9 (FAS, 95 % CI, 6.1, 9.8) months. The monotherapy study (n = 63) resulted in an ORR of 28.57 % (FAS, 95 % CI, 18.4, 40.6) and a median PFS of 5.4 (FAS, 95 % CI, 2.9, 9.8) months. In both studies, common toxicities associated with utidelone administration included peripheral neuropathy, fatigue, myalgia, and arthralgia, but the toxicities were limited and manageable. Notably, very mild myelosuppression, low liver and renal toxicities, and very limited gastrointestinal toxic effect were observed, in contrast to other agents in the same class. CONCLUSIONS: Utidelone showed promising efficacy, tolerability, and advantageous safety profiles in the treatment of patients with advanced anthracycline/taxane-refractory metastatic breast cancer and may offer new treatment options to overcome drug resistance. TRIAL REGISTRATION: CHiCTR-TRC-13004205 , registered on August 15, 2013.

[A multicenter, randomized, controlled, phase â ¢ clinical study of PEG-rhG-CSF for preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer].

OBJECTIVE: To explore the safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer (NSCLC), and to provide the basis for clinical application. METHODS: According to the principle of open-label, randomized, parallel-group controlled clinical trial, all patients were randomized by 1∶1∶1 into three groups to receive PEG-rhG-CSF 100 µg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 µg/kg, respectively. The patients with breast cancer received two chemotherapy cycles, and the NSCLC patients received 1-2 cycles of chemotherapy according to their condition. All patients were treated with the combination chemotherapy of TAC (docetaxel+ epirubicin+ cyclophosphamide) or TA (docetaxel+ epirubicin), or the chemotherapy of docetaxel combined with carboplatin, with a 21 day cycle. RESULTS: The duration of grade 3-4 neutropenia in the PEG-rhG-CSF 100 µg/kg and PEG-rhG-CSF 6 mg groups were similar with that in the rhG-CSF 5 µg/kg group (P>0.05 for all). The incidence rate of grade 3-4 neutropenia in the PEG-rhG-CSF 100 µg/kg group, PEG-rhG-CSF 6 mg group, and G-CSF 5 µg/kg group were 69.7%, 68.4%, and 69.5%, respectively, with a non-significant difference among the three groups (P=0.963). The incidence rate of febrile neutropenia in the PEG-rhG-CSF 100 µg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 µg/kg group were 6.1%, 6.4%, and 5.5%, respectively, showing no significant difference among them (P=0.935). The incidence rate of adverse events in the PEG-rhG-CSF 100 µg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 µg / kg group were 6.7%, 4.1%, and 5.5%, respectively, showing a non-significant difference among them (P=0.581). CONCLUSIONS: In patients with breast cancer and non-small cell lung cancer (NSCLC) undergoing TAC/TA chemotherapy, a single 100 µg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF at 48 hours after chemotherapy show definite therapeutic effect with a low incidence of adverse events and mild adverse reactions. Compared with the continuous daily injection of rhG-CSF 5 µg/kg/d, a single 100 µg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF has similar effect and is more advantageous in preventing chemotherapy-induced neutropenia.

[Efficacy and safety of rh-endostatin combined with docetaxel in second-line or intolerant toxicity for first-line treatment in patients with advanced non-small cell lung cancer].

OBJECTIVE: To analyze the efficacy and safety of combination of rh-endostatin (Endostar) with docetaxel treatment on patients of non-small cell lung cancer (NSCLC) who presented PD or intolerable toxicity in/after first-line chemotherapy. METHODS: A randomized, double-blind, placebo-controlled and multi-center clinical trial was conducted. Patients with stage IIIB/IV of NSCLC experienced previous chemotherapy of one-regimen were screened for this trial. A total of 68 cases were included in this study. Single docetaxel and that combined with endostar were conducted in two arms. The response, time to progression (TTP) and adverse effects were observed in both arms. RESULTS: The objective response rate (ORR) and clinical benefit rate (CBR) were 0 and 62.5% in the combined arm, along with 0 and 53.3% in the single docetaxel arm, with a non-significant difference between the two groups (all P > 0.05), respectively. The median TTPs in the combined and single docetaxel arms were 2.63 and 2.07 months, respectively (P = 0.079). The median TTPs of the participants with progressive disease (PD) after first-line chemotherapy were 1.33 and 1.67 months in the combined and single docetaxel arms, respectively (P = 0.946). The median TTPs of the participants with intolerant adverse effects in first-line chemotherapy were 4.70 months and 3.17 months in the combined and single docetaxel arms, respectively (P = 0.070). The median TTPs of the patients with SD after 2 therapeutic cycles in the combined and single docetaxel arms were 6.23 months and 3.27 months, respectively (P = 0.040). The differences between two arms were non-significant in adverse, serious adverse and cardiovascular adverse effects (all P > 0.05). CONCLUSIONS: Endostar may prolong TTP in patients with advanced NSCLC benefited from docetaxel treatment without increased toxicities.

Pegylated filgrastim is comparable with filgrastim as support for commonly used chemotherapy regimens: a multicenter, randomized, crossover phase 3 study.

The purpose of this study was to compare the efficacy and safety of a single subcutaneous injection of pegylated filgrastim with daily filgrastim as a prophylaxis for neutropenia induced by commonly used chemotherapy regimens. Fifteen centers enrolled 337 chemotherapy-naive cancer patients with normal bone marrow function. All patients randomized into AOB and BOA arms received two cycles of chemotherapy. Patients received a single dose of pegylated filgrastim 100 µg/kg in cycle 1 (AOB) or cycle 2 (BOA) and daily doses of filgrastim 5 µg/kg/day in cycle 1 (BOA) or cycle 2 (AOB). Efficacy and safety parameters were recorded. The primary end point was the rate of protection against grade 4 neutropenia after chemotherapy [defined as the rate at which the absolute neutrophil count (ANC) remained >0.5×10(9)/l throughout the entire cycle]. Ninety-four percent of patients receiving pegylated filgrastim or filgrastim did not develop grade 4 neutropenia. The incidence of ANC<1.0×10(9)/l was 16.0% (50/313) after support with either pegylated filgrastim or filgrastim. The incidences of febrile neutropenia and antibiotic administration were similar in both groups. Notably, faster ANC recovery was observed with pegylated filgrastim support. The ANC nadir was also earlier with pegylated filgrastim (day 7) support than with filgrastim support (day 9), although the depth of nadir was not significantly different. A single subcutaneous injection of pegylated filgrastim 100 µg/kg provided adequate and safe neutrophil support comparable with daily subcutaneous injections of unmodified filgrastim 5 µg/kg/day in patients receiving commonly used standard-dose mild-to-moderate myelosuppressive chemotherapy regimens.

Multicenter clinical study for evaluation of efficacy and safety of transdermal fentanyl matrix patch in treatment of moderate to severe cancer pain in 474 chinese cancer patients.

OBJECTIVE: Although a new matrix formulation fentanyl has been used throughout the world for cancer pain management, few data about its efficacy and clinical outcomes associated with its use in Chinese patients have been obtained. This study aimed to assess the efficacy and safety of the new system in Chinese patients with moderate to severe cancer pain. METHODS: A total of 474 patients with moderate to severe cancer pain were enrolled in this study and were treated with the new transdermal fentanyl matrix patch (TDF) up to 2 weeks. All the patients were asked to record pain intensity, side effects, quality of life (QOL), adherence and global satisfaction. The initial dose of fentanyl was 25 µg/h titrated with opioid or according to National Comprehensive Cancer Network (NCCN) guidelines. Transdermal fentanyl was changed every three days. RESULTS: After 2 weeks. The mean pain intensity of the 459 evaluated patients decreased significantly from 5.63±1.26 to 2.03±1.46 (P<0.0001). The total remission rate was 91.29%, of which moderate remission rate 53.16%, obvious remission rate 25.49% and complete remission rate 12.64%. The rate of adverse events was 33.75%, 18.78% of which were moderate and 3.80% were severe. The most frequent adverse events were constipation and nausea. No fatal events were observed. The quality of life was remarkably improved after the treatment (P<0.0001). CONCLUSION: The new TDF is effective and safe in treating patients with moderate to severe cancer pain, and can significantly improve the quality of life.

[Randomized phase II trial on escalated doses of Rh-endostatin (YH-16) for advanced non-small cell lung cancer].

OBJECTIVE: To investigate the response rate (RR), time to tumor progression (TTP), quality of life (QOL) and adverse reaction in the treatment of pretreated advanced non-small cell lung cancer (NSCLC) using escalated doses of rh-endostatin (YH-16), and to determine the optimal dose for clinical application. METHODS: In this phase II randomized, controlled, multicenter trial, the patients were randomly divided into two groups to receive daily 3 hours intravenous infusion of either 7.5 mg x m(-2) or 15 mg/m(2) YH-16 for 28 days. RESULTS: Totally, 68 patients were entered and 60 patients were evaluable. There were no differences in RR (3.0% in both groups, P > 0.05), median TTP (ITT: 60 days versus 71 days, P > 0.05), QOL and incidence rate of adverse reactions (48.6% versus 38.7%, P > 0.05). No significant unexpected adverse events were observed. CONCLUSION: Rh-endostatin may have anti-tumor activity with high clinical benefit rate and is well tolerated in pretreated advanced NSCLC patients. The dose of 7.5 mg x (m(2))(-1) x d(-1) is clinically recommended.

[Results of randomized, multicenter, double-blind phase III trial of rh-endostatin (YH-16) in treatment of advanced non-small cell lung cancer patients].

BACKGROUND: Endostar™ (rh-endostatin, YH-16) is a new recombinant human endostatin developed by Medgenn Bioengineering Co. Ltd., Yantai, Shandong, P.R.China. Pre-clinical study indicated that YH-16 could inhibit tumor endothelial cell proliferation, angiogenesis and tumor growth. Phase I and phase II studies revealed that YH-16 was effective as single agent with good tolerance in clinical use.The current study was to compare the response rate , median ti me to progression (TTP) ,clinical benefit andsafety in patients with advanced non-small cell lung cancer ( NSCLC) , who were treated with YH-16 plus vi-norelbine and cisplatin (NP) or placebo plus NP. METHODS: Four hundred and ninety-three histologically or cy-tologically confirmed stage IIIB and IV NSCLC patients , withlife expectancy > 3 months and ECOG perform-ance status 0-2 , were enrolledin a randomized ,double-blind ,placebo-controlled , multicenter trial ,either trialgroup : NP plus YH-16 (vinorelbine 25 mg/m² on day 1 and day 5 ,cisplatin 30mg/m² on days 2 to 4 , YH-167.5mg/m² on days 1 to 14) or control group : NP plus placebo (vinorelbine 25 mg/m² on day 1 and day 5 ,cis-platin 30 mg/m² on days 2 to 4 ,0.9% sodium-chloride 3 .75 ml on days 1 to 14) every 3 weeks for 2-6 cycles .The trial endpoints included response rate ,clinical benefit rate ,time to progression,quality of life and safety . RESULTS: Of 486 assessable patients , overall response rate was 35.4% in trial group and 19.5% in controlgroup (P=0 .0003) . The median TTP was 6 .3 months and 3 .6 months for trial group and control group respectively (P < 0 .001) . The clinical benefit rate was 73 .3 %in trial group and 64.0% in control group (P=0 .035) .In untreated patients of trial group and control group ,the response rate was 40 .0% and 23.9%(P=0 .003) ,the clinical benefit rate was 76 .5 % and 65 .0 % (P=0 .023) ,the median TTP was 6 .6 and 3 .7months (P=0 .0000) ,respectively .In pretreated patients of trial group and control group ,the response ratewas 23.9% and 8.5%(P=0 .034) ,the clinical benefit rate was 65.2% and 61.7%(P=0 .68) ,the median TTP was 5 .7 and 3 .2 months (P=0 .0002) ,respectively . The relief rate of clinical symptoms in trial groupwas higher than that of those in control group ,but no significance existed (P > 0 .05) . The score of quality oflife in trial group was significantly higher than that in control group (P=0 .0155) after treatment . There were no significant differences in incidence of hematologic and non-hematologic toxicity , moderate and severe sideeffects betweentrial group and control group . CONCLUSIONS: The addition of YH-16 to NP regimen results in significantly and clinically meaningful improvement in response rate , median time to tumor progression,and clinical benefit rate compared with NP alone in advanced NSCLC patients . YH-16 in combination with chemotherapy shows a synergic activity and a favorable toxic profile in advanced cancer patients .

[Clinical research of taxotere in treatment of metastatic breast cancer].

BACKGROUND & OBJECTIVE: Recently, high-dose docetaxel has been proved to be an effective antineoplastic drug in the treatment of metastatic breast cancer.However,there was a few reports about moderate-dose docetaxel and Adriamycin in the treatment of metastatic breast cancer. This study was designed to observe the response rate and toxic reaction of Taxotere and Taxotere plus Adriamycin in the treatment of metastatic breast cancer. METHODS: From September 1996 to April 2000, 34 cases with metastatic breast cancer, which were treated in Department of Oncology, The Second Central Hospital in Tianjin, were included in the study. For group A (14 cases), Taxotere single agent was administered at a dose of 75 mg/m(2) iv 1 hour. For group B, Taxotere was administered at a dose of 60 mg/m(2) combined with Adriamycin 50 mg/m(2) i.v. 1 hour. The same schedule for both groups was repeated every 21 days, with three cycles for all patients. RESULTS: The recent response rates of group A and group B were 57.14% (8/14) and 75.0% (15/20), respectively. The 2-and 4-year survival rates were 35.7%, 14.3% for group A, and 40.0%, 15.0% for group B. The median overall survival durations of group A and group B were 22 months and 23 months. The median overall response durations of these two groups were 10 and 11 months, respectively. The main adverse reactions of these two groups were neutropenia, nausea, vomiting, stomatitis, diarrhea, alopecia, fatigue, myalgia, fluid retention, and skin flushing. Grade 3 and grade 4 neutropenia occurred in group A and group B were 57.1% (8/14) and 70.0% (14/20), respectively. CONCLUSION: Taxotere is effective in the treatment of metastatic breast cancer. The toxic reactions are tolerable.