Safety Of Vinorelbine Research Articles

433P Effectiveness and safety of vinorelbine + inetetamab + pyrotinib in ≥second-line treatment of HER2-positive metastatic breast cancer

433P Effectiveness and safety of vinorelbine + inetetamab + pyrotinib in ≥second-line treatment of HER2-positive metastatic breast cancer

Efficacy and safety of vinorelbine and cisplatin regimen of different doses and intensities for neoadjuvant chemotherapy in patients with locally advanced esophageal carcinoma.

BackgroundThere are few studies focused on comparing the toxicity, postoperative complication rate, and survival among patients with locally advanced esophageal squamous cell cancer receiving a different dose and intensity of vinorelbine plus cisplatin for neoadjuvant chemoradiotherapy (nCRT) followed by surgery.MethodsIn total, 78 patients diagnosed with locally advanced esophageal squamous cell cancer that had received a vinorelbine and cisplatin (VP)1 or VP2 regimen for nCRT followed by surgery in Taizhou Hospital of Zhejiang Province between June 2008 and December 2016 were retrospectively analyzed. The VP1 regimen involved cisplatin 75 mg/m2 on day 1, and vinorelbine 25 mg/m2 on days 1 and 8, for two cycles. The VP2 regimen involved cisplatin 25 mg/m2 on days 1 to 4, and vinorelbine 25 mg/m2 on days 1 and 8, for two cycles. The rate of adverse events, postoperative complications, and survival were compared between the two groups.ResultsThe median overall survival (OS) was 97.6 months (85.6–109.7) in the VP2 group, which was not significantly different to that of the VP1 group [hazard ratio (HR), 1.008 (0.999–1.108); P=0.509]. The main toxicity was hematologic adverse events. The VP2 group had significantly higher rates of all grades of anemia, leukopenia, neutropenia, and thrombocytopenia (all P<0.05), as well as grade 3 or 4 of leukopenia and neutropenia (P<0.05) compared to the VP1 group. Regarding postoperative complications, the VP2 group had a significantly higher rate of pulmonary infection than the VP1 group (P<0.05).ConclusionsCompared with VP2, VP1 showed comparable efficacy in terms of survival, with less hematologic toxicity and postoperative pulmonary infection. Therefore, we recommended that VP1 over VP2 to be the optimized VP neoadjuvant chemotherapy regimen for locally advanced esophageal squamous cell cancer.

Efficacy and safety of vinorelbine in heavily pretreated recurrent/metastatic head and neck squamous cell carcinoma patients.

The aim of this study was to evaluate the efficacy and tolerance of vinorelbine as a single agent in the treatment of recurrent/metastatic head and neck squamous cell carcinoma. Patients were treated with oral or intravenous vinorelbine according to the pluridisciplinary tumor board's decision. Efficacy and safety outcomes were analyzed retrospectively. Twenty-three patients were included in the study. Sixteen patients (69%) had received at least two previous lines of chemotherapy. The disease control rate was 19%. The median progression-free survival was 2.6 months and the median overall survival was 3.4 months. The rate of grade 3-4 side effects was low (13%). Only one patient discontinued treatment because of side effects. Vinorelbine seems to be a well-tolerated regimen in heavily pretreated patients. However, this regimen does not seem to be efficient enough to be recommended.

Assessment on the Efficacy and Safety of Aidi Injection Combined with Vinorelbine and Cisplatin for Treatment of Advanced Nonsmall Cell Lung Cancer.

Background:The aim of this study was to assess the efficacy and safety of vinorelbine and cisplatin (NP chemotherapy) alone or in combination with Aidi injection for the treatment of advanced nonsmall cell lung cancer (NSCLC).Methods:Pertinent publications were identified in PubMed, EMBASE, Cochrane Library, CNKI, CQVIP, and Wanfang databases, up to December 8, 2015. After quality assessment of all included randomized controlled trials evaluating Aidi injection combined with NP chemotherapy for the treatment of advanced NSCLC, a meta-analysis was performed by Review Manager 5.2 and STATA 12.0 for statistical analyses.Results:Twelve studies including 509 and 503 cases in the experimental and control groups, respectively, were finally analyzed. The meta-analysis revealed that when cisplatin dose ranging from 20 to 40 mg/m2, combination of Aidi injection and NP chemotherapy was statistically different compared with NP chemotherapy alone in enhancing efficiency (relative risk [RR] = 1.24, 95% confidence interval [CI] [1.05–1.47], P = 0.010) and reducing the incidence of Grade II or above nausea and vomiting (RR = 0.49, 95% CI [0.30–0.80], P = 0.005). Meanwhile, with cisplatin ranging from 80 to 120 mg/m2, no significant differences in efficiency (RR = 1.11, 95% CI [0.87–1.42], P = 0.390) and Grade II or above nausea and vomiting (RR = 0.88, 95% CI [0.71–1.10], P = 0.260) were obtained. In addition, Aidi injection combined with NP chemotherapy was superior to NP chemotherapy alone in improving the quality of life, alleviating Grade II or above leukopenia and thrombocytopenia.Conclusions:Aidi injection combined with NP chemotherapy can enhance efficiency, improve the quality of life, and decrease adverse effects in patients with advanced NSCLC.

Phase II study of gemcitabine and vinorelbine as second- or third-line therapy in patients with primary refractory or platinum-resistant recurrent ovarian and primary peritoneal cancer by the Korean Cancer Study Group (KCSG)_KCSG GY10-10

ObjectiveThe main aim of this study was to evaluate the antitumor activity and safety of vinorelbine and gemcitabine combination chemotherapy in patients with primary refractory or recurrent platinum-resistant epithelial ovarian and primary peritoneal cancers. MethodsPatients with platinum-resistant or primary refractory disease were eligible. Patients were allowed one prior chemotherapy for the treatment of platinum-resistant or refractory disease. Vinorelbine 25mg/m2, followed by gemcitabine 1000mg/m2, was administered intravenously on days 1 and 8 every 3weeks. Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 and cancer antigen 125 test (CA-125 criteria) were adopted to classify responses. Results44 patients received the median of 4 (range, 1–24) treatments with fifteen (34.1%) receiving six or more cycles. The overall objective response rate was 22.7%. One patient (2.3%) had complete while 9 patients (20.4%) had partial responses with median duration of response of 5.9months. 17 patients (38.6%) had stable disease for a median of 3.3months. Median progression-free survival (PFS) was 3.4months and overall survival (OS) was 14.5months. Four (9.1%) patients were not assessable. Neutropenia was the most frequently encountered toxicity, with grade 3 or 4 observed in 22 patients (50.0%). Fifteen patients (34.1%) needed immediate dose reduction. No treatment related death was reported. ConclusionsThe combination chemotherapy with gemcitabine and vinorelbine achieved the primary end point of our clinical trial in management of platinum resistant recurrent ovarian cancer. However, further sophisticated dosing and scheduling of combination chemotherapy are needed because of a significant proportion of dose reduction.

Phase II study of vinorelbine and capecitabine as first-line treatment for metastatic breast cancer.

e12004 Background: Vinorelbine (V) and capecitabine (C) are likely to have a synergisitic interaction. Vinorelbine upregulates thymidine phosphorylase; a key enzyme in the conversion of capecitabine to active 5-FU in tumor tissue. Available phase II clinical data reports response rates ranging from 48-70% in first line metastatic breast cancer (MBC) for this combination. We evaluated the efficacy and safety of vinorelbine plus capecitabine in patients with MBC relapsing after adjuvant anthracycline based treatment. Methods: Sixty patients were enrolled between Oct 2008 through Dec 2010. All patients had measurable MBC relapse after adjuvant anthracycline and/or taxanes, WHO PS &lt; 2, adequate bone marrow, renal and hepatic functions. Patients received intravenous vinorelbine 25 mg/m2 on day 1 and 8 and oral capecitabine 1000 mg/m2 bid on days 1 to 14, cycles to be repeated every 3 weeks. Patients with PD went off the study while those with CR, PR or SD continued treatment for a maximum of 8 cycles. Results: Median age 54 years (range 35-67 years), Median WHO PS 0 (range 0-1). Previous adjuvant therapy anthracycline (100%) and hormone therapy (60%). Median disease free interval was 6 months. Main metastatic sites were lung (40%), liver (25%), bone (40%) skin (35%), and lymph nodes (35%). Twenty five percent of patients had one metastatic site, 60% had two sites, 10% had three sites and 5% had more than three sites. The total number of cycles delivered was 441 with a median number of cycles/patients of 7 (range 3-8). An objective tumor response was achieved in 36 pts (60%), complete response (CR) in 6 pts (10%), 12 pts (20%) had stable disease (SD). After a follow up period of 6-36 months, the median time to progression and median survival were 14 and 23 months, respectively. No WHO G4 toxicities were noted, 3 pts (5%) developed G3 neutropenia and one patient (1.7%) developed G3 hand and foot syndrome. G2 anemia, neutropenia and diarrhea were reported in 2 pts (3.3%), 3 pts (5%) and 6 pts (10%), respectively. Conclusions: The combination of vinorelbine and capecitabine showed significant efficacy and mild toxicity as a first-line treatment for patients with metastatic breast cancer after failure of adjuvant anthracycline based therapy.

PO-113: Activity and Safety of Vinorelbine in Adenoid Cystic Carcinoma: A Single Institution Retrospective Case Series

PO-113: Activity and Safety of Vinorelbine in Adenoid Cystic Carcinoma: A Single Institution Retrospective Case Series

Clinical research of the combination of vinorelbine and ifosfamide in the treatment of advanced breast cancer resistant to anthracycline and taxane

Objective To observe and compare efficacy and safety of vinorelbine (NVB) plus ifosfamide (IFO) (NI regimen) and NVB plus cisplatin(DDP) (NP regimen) in treatment of metastatic breast cancer.Methods 82 cases of recurrent and metastatic breast cancer after the failure of treatment with anthracyclines and taxanes,40 cases were treated with NI regimen (NVB 25 mg/m2,day 1,day 8,IFO 1.2 g/m2,day 1,day 2,day 3),and the other 42 cases received NP regimen (NVB 25 mg/m2,day 1,day 8,DDP 25 mg/m2,day 1,day 2,day 3).Both groups were constituted of 21 days one cycle.After 2 cycles of chemotherapy,the response rate and side effects were evaluated.Results All 82 cases were evaluated for objective response.The total response rate of NI group and NP group were 52.50 ％ (21/40) and 57.14 ％ (24/42).There was no significiant difference (P ＞ 0.05).By analysis of the correlative factors,the total response rate in treatment of triple-negative breast cancer of NI group was 43.75 ％ (7/16),and that of NP group was 44.44 ％ (8/18).The two rates were also approximative (P ＞ 0.05).Main side effects were both bonemarrow suppression and gastrointestinal reaction.Bonemarrow suppression rate at grade Ⅲ-Ⅳ of NI group [57.5 ％ (23/40)] had no significant difference compared with that of NP group[57.14 ％ (24/42)] (P ＞ 0.05).But grade Ⅲ-Ⅳ gastrointestinal rate of NI group [7.50 ％ (3/40)] was significantly lower than that of NP group [26.19％(11/42)](P ＜ 0.05).Conclusion NI regimen in treatment of advanced breast cancer is effective,and it shows a similar response rate compared with NP regimen.Also it is effective for triple negeative breast cancers.The toxicity can be tolerated,and the gastrointestinal reaction rate of NI regimen is lower.NI regimen is a good choose in treatment of advanced breast cancer. Key words: Breast neoplasms; Drug therapy, combination; Advanced stage

Vinorelbine for non-small cell lung cancer

Importance of the field: Vinorelbine is a ‘third-generation’ vinca alkaloid approved for the treatment of NSCLC. The introduction of ‘third-generation’ drugs (vinorelbine, gemcitabine, taxanes) in platinum combination improved survival of patients with advanced NSCLC, with substantially similar results among the different drugs. Treatment toxicities are considerable in this setting.Areas covered in this review: This narrative review reports a synthesis of evidence available from published clinical trials, systematic reviews and meta-analyses on the activity and safety of vinorelbine, used as single agent or in combination chemotherapy in patients with NSCLC, from 1990 to 2009.What the reader will gain: When vinorelbine was administered in a weekly schedule without interruptions, the most common toxicity was neutropenia that often precluded administration of the drug, therefore, reducing the dose intensity. A schedule providing administration of vinorelbine on days 1 and 8 every 3 weeks seemed to improve the tolerability of the drug. Tolerability of the drug did not result lower in the elderly subset. None of the other ‘third-generation’ drugs were clearly better tolerated than vinorelbine. Moreover, in the adjuvant setting, vinorelbine is the only third-generation drug that demonstrated, in combination with cisplatin, a consistent improvement in survival on a long-term basis.Take home message: Vinorelbine is an active and generally manageable therapeutic option for the treatment of both early and advanced NSCLC.

Phase II trial of vinorelbine and trastuzumab in patients with HER2-positive metastatic breast cancer. A prospective, open label, non-controlled, multicenter phase II trial (to investigate efficacy and safety of this combination chemotherapy)

The purpose of this study was to evaluate the efficacy (progression free survival (PFS) and response rate) and safety of vinorelbine and trastuzumab combination chemotherapy in patients with HER2-overexpressing, metastatic breast cancer as a first line chemotherapy regimen. Patients with histologically confirmed, HER2-positive (immunohistochemistry (ICH) 3+, or 2+ and FISH+) metastatic breast cancer who had nor received prior vinorelbine or anti-HER2 therapy in the adjuvant setting, received at least eight weeks of vinorelbine i.v. (25 mg/g weekly) and trastuzumab (4 mg/kg on day 1 followed by 2 mg/kg weekly). Forty-one women from six participating centers were enrolled into the trial. The overall response rate, was 43.9% (18 of 41 patients), (CI 28-60.3%), 30% of patients were progression free after 1 year. Four patients reached complete remission, 14 partial remission and five had stable disease for at least 18 weeks. Six patients developed primary progression. 35 patients (85%) experienced progression after a median time of 235 days. Therapy was in general well-tolerated. There were two CTC grade 4 infusion syndromes and two patients experienced cardiotoxicity at least grade 2. This phase II trial of vinorelbine and trastuzumab demonstrated an effective and well-tolerated regimen with a favourable safety profile.

Activity and safety of vinorelbine and capecitabine as first-line treatment in patients with metastatic breast cancer – a phase II trial

Activity and safety of vinorelbine and capecitabine as first-line treatment in patients with metastatic breast cancer – a phase II trial

Late Phase II Clinical Study of Vinorelbine Monotherapy in Advanced or Recurrent Breast Cancer Previously Treated with Anthracyclines and Taxanes

At present, it is one of the most important issues for the treatment of breast cancer to develop the standard therapy for patients previously treated with anthracyclines and taxanes. With the objective of determining the usefulness of vinorelbine monotherapy in patients with advanced or recurrent breast cancer after standard therapy, we evaluated the efficacy and safety of vinorelbine in patients previously treated with anthracyclines and taxanes. Vinorelbine was administered at a dose level of 25 mg/m(2) intravenously on days 1 and 8 of a 3 week cycle. Patients were given three or more cycles in the absence of tumor progression. A maximum of nine cycles were administered. The response rate in 50 evaluable patients was 20.0% (10 out of 50; 95% confidence interval, 10.0-33.7%). Responders plus those who had minor response (MR) or no change (NC) accounted for 58.0% [10 partial responses (PRs) + one MR + 18 NCs out of 50]. The Kaplan-Meier estimate (50% point) of time to progression (TTP) was 115.0 days. The response rate in the visceral organs was 17.3% (nine PRs out of 52). The major toxicity was myelosuppression, which was reversible and did not require discontinuation of treatment. The results of this study show that vinorelbine monotherapy is useful in patients with advanced or recurrent breast cancer previously exposed to both anthracyclines and taxanes.

Interim results of a prospective, open-label, multicentre phase II trial of the efficacy and safety of vinorelbine (N) and trastuzumab (H) in patients with HER2-positive metastatic breast cancer (MBC)

831 Background: Preclinical data indicate that H and N have synergistic activity. This observation has prompted a number of clinical studies of this combination in women with HER2-positive MBC. H plus N has been shown to be active, producing response rates of up to 84% when used first line, and well tolerated. We are conducting a phase II study to further evaluate this combination. Methods: Women with histologically confirmed, HER2-positive (IHC 3+, or 2+ and FISH positive) MBC who had not received prior N or anti-HER2 therapy were eligible. Patients with active heart disease or with clinical manifest CNS metastases were excluded. Women received N 25mg/m2 weekly and H 4mg/kg loading dose followed by 2mg/kg weekly for at least 8 weeks and thereafter until progression. Results: 26 of a target enrolment of 32 patients have been enrolled: median age 58 (range 3175) years; median Karnofsky performance status 90% (70100). Median duration of therapy is currently 15.6 (0.129.3+) weeks; 11 patients remain on therapy. The overall response rate is 50% (2 CR, 11 PR), with 5 of 26 patients not evaluable (RR in evaluable patients, 61.9%); 2 patients had stable disease and 6 progressive disease as their best response. Treatment was well tolerated, with adverse events being mainly mild to moderate in severity and as expected based on the known side effects of these agents: fatigue 50%; nausea 34.6%; diarrhoea 23.1%; vomiting 19.2%. The majority of patients experienced neutropenia (53.8%), anaemia (76.9%) or leucopenia (73.1%); 6 patients had grade 3 or 4 neutropenia. 6 patients experienced 10 serious adverse events, including 2 infusion-related reactions and 2 cases of dyspnoea with the initial trastuzumab infusion, and one decrease in LVEF to below 50%. Conclusions: This interim analysis of a phase II study of H and N supports previous trials demonstrating that this combination is an effective and well-tolerated regimen for the treatment of women with HER2-positive metastatic breast cancer. Enrolment continues and updated data will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche

Interim results of a prospective, open-label, multicentre phase II trial of the efficacy and safety of vinorelbine (N) and trastuzumab (H) in patients with HER2-positive metastatic breast cancer (MBC)

831 Background: Preclinical data indicate that H and N have synergistic activity. This observation has prompted a number of clinical studies of this combination in women with HER2-positive MBC. H plus N has been shown to be active, producing response rates of up to 84% when used first line, and well tolerated. We are conducting a phase II study to further evaluate this combination. Methods: Women with histologically confirmed, HER2-positive (IHC 3+, or 2+ and FISH positive) MBC who had not received prior N or anti-HER2 therapy were eligible. Patients with active heart disease or with clinical manifest CNS metastases were excluded. Women received N 25mg/m2 weekly and H 4mg/kg loading dose followed by 2mg/kg weekly for at least 8 weeks and thereafter until progression. Results: 26 of a target enrolment of 32 patients have been enrolled: median age 58 (range 3175) years; median Karnofsky performance status 90% (70100). Median duration of therapy is currently 15.6 (0.129.3+) weeks; 11 patients remain on therapy. The overall response rate is 50% (2 CR, 11 PR), with 5 of 26 patients not evaluable (RR in evaluable patients, 61.9%); 2 patients had stable disease and 6 progressive disease as their best response. Treatment was well tolerated, with adverse events being mainly mild to moderate in severity and as expected based on the known side effects of these agents: fatigue 50%; nausea 34.6%; diarrhoea 23.1%; vomiting 19.2%. The majority of patients experienced neutropenia (53.8%), anaemia (76.9%) or leucopenia (73.1%); 6 patients had grade 3 or 4 neutropenia. 6 patients experienced 10 serious adverse events, including 2 infusion-related reactions and 2 cases of dyspnoea with the initial trastuzumab infusion, and one decrease in LVEF to below 50%. Conclusions: This interim analysis of a phase II study of H and N supports previous trials demonstrating that this combination is an effective and well-tolerated regimen for the treatment of women with HER2-positive metastatic breast cancer. Enrolment continues and updated data will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche

Vinorelbine and cisplatin in metastatic squamous cell carcinoma of the oesophagus: response, toxicity, quality of life and survival

BackgroundVinorelbine and cisplatin are active against squamous cell oesophageal carcinoma. The purpose of this phase II study was to evaluate the efficacy and safety of vinorelbine plus cisplatin in previously untreated patients with metastatic squamous cell oesophageal carcinoma and to estimate the progression-free survival, overall survival and quality of life (QoL) of the patient population. Patients and methodsSeventy-one eligible patients were entered into a study of vinorelbine 25 mg/m2 on days 1 and 8 plus cisplatin 80 mg/m2 on day 1, every 3 weeks. Degree of dysphagia relief was monitored and QoL was measured using the EORTC QLQ-C30. ResultsAll eligible patients were assessed for response and 24 achieved a confirmed partial response (33.8%; 95% confidence interval 23–46); the median duration of response was 6.8 months, progression-free survival was 3.6 months and median survival of the whole group was 6.8 months. Toxicity was mainly related to neutropenia (grade 3/4 in 41% of patients). At cycle 2, 43% of the patients reported at least a moderate improvement in global health status/QoL and 25% experienced a large improvement. ConclusionsVinorelbine plus cisplatin represents a well-tolerated active palliative regimen for patients with advanced squamous cell carcinoma of the oesophagus. This combination may offer a better therapeutic index than cisplatin–5-fluorouracil.

Phase II Trial of Vinorelbine in Recurrent and Progressive Epithelial Ovarian Cancer

Objective.A phase II, multicenter trial was conducted to define the efficacy and safety of vinorelbine (Navelbine (vinorelbine tartrate) injection, NVB) in the treatment of advanced epithelial ovarian cancer (EOC).Methods.Patients with persistent or recurrent EOC who had received one prior platinum-based chemotherapy regimen were eligible. NVB was administered at 30 mg/m2as a weekly outpatient intravenous infusion.Results.Using an intent-to-treat analysis of the 38 patients who received at least one dose, 11(29%, 95% confidence limits 15–46%) objective responses (4 complete, 7 partial) were observed. The median duration of response was 19 weeks. For all 38 patients, the median time to treatment failure and median survival were 12 and 60 weeks, respectively. Four of the 12 patients with platinum-resistant disease responded, while 7 of the 24 patients with platinum-sensitive disease responded. Toxicity was evaluable in all 38 patients. During course 1, 15 patients required dose reduction and 21 required dose delays. Grade 3–4 granulocytopenia occurred in 23 (62%) of 37 reporting patients. Grade 3–4 anemia and thrombocytopenia occurred in 16 and 5%, respectively. The most common nonhematologic toxicities were nausea (grade 3 or less, in 34%), constipation (grade 3 or less, in 29%), and asthenia (grade 2 or less, in 24%). No life-threatening adverse effects were reported.Conclusions.NVB is an effective, palliative agent for women with recurrent EOC. Dose-limiting granulocytopenia is substantial, yet manageable.

Efficacy and safety of vinorelbine in elderly patients (aged > 70 years) with advanced NSCLC

Efficacy and safety of vinorelbine in elderly patients (aged > 70 years) with advanced NSCLC

Vinorelbine monochemotherapy in non-small-cell lung cancer: Experience in patients with low performance status: Masotti A, Zannini G, Poggi R, Morandini G.C. Pneumology Division, Ospedale Maggiore, ULSS 25, Verona. Monaldi Arch Chest Dis 1994;49:197–200

The aim of this study was to investigate the activity and safety of vinorelbine in patients with low performance status. From March 1992 to June 1993 we studied 14 untreated patients with Stage IV non-small-cell lung cancer (NSCLC) and a "performance status" lower than 70% of the Karnofsky score. Treatment was by means of an intravenous administration of vinorelbine (30 mg.m-2) repeated weekly. On the whole, the toxicity was mild. Of 150 cycles administered, we observed 10 cases of Grade 3 leucopenia and 4 cases of Grade 4 leucopenia. A peripheral neurotoxicity (Grade 2-3) was reported in two patients. The objective response rate was 36% partial response. Our data suggest that vinorelbine could be an active and safe treatment for those patients who cannot receive polychemotherapy because of low performance status, and justify further larger studies comparing vinorelbine, either as a single agent or in combination, to other analogues or to assess its efficacy in supportive care.