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Cancer Biotherapy & Radiopharmaceuticals Jun 2023This study evaluated the efficacy and safety between 8 spheres plus bronchial arterial infusion (BAI) cisplatin and intravenous vinorelbine plus cisplatin as third-line...
This study evaluated the efficacy and safety between 8 spheres plus bronchial arterial infusion (BAI) cisplatin and intravenous vinorelbine plus cisplatin as third-line treatments in locally advanced non-small cell lung cancer (NSCLC) patients. Totally, 56 locally advanced NSCLC patients with second-line chemotherapy failure were recruited. Then, 28 patients received 8 spheres plus BAI cisplatin treatment, and another 28 patients received intravenous vinorelbine plus cisplatin treatment. In general, 8 spheres plus BAI cisplatin increased objective response rate (57.2% vs. 17.8%, = 0.002) and disease control rate (78.6% vs. 42.8%, = 0.003) compared with intravenous vinorelbine plus cisplatin; meanwhile, it also elevated quality of life (QOL) score (46.7 ± 7.1 vs. 41.5 ± 5.2, = 0.003) compared with intravenous vinorelbine plus cisplatin. Furthermore, 8 spheres plus BAI cisplatin prolonged progression-free survival (PFS) (median [95% confidence interval, CI]: 7.9 [6.3-9.5] months vs. 4.3 [3.5-5.1] months, < 0.001) and overall survival (OS) (median [95% CI]: 14.6 [11.0-18.2] months vs. 10.5 [10.2-10.8] months, = 0.029) compared with intravenous vinorelbine plus cisplatin, which was further supported by multivariate Cox's regression analysis (PFS: < 0.001; OS: = 0.007). In addition, subgroup analyses revealed that 8 spheres plus BAI cisplatin markedly elevated treatment response, QOL, and survival compared with intravenous vinorelbine plus cisplatin in squamous cell carcinoma patients, but not in adenomatous carcinoma and adenosquamous carcinoma patients. Regarding safety, 8 spheres plus BAI cisplatin exhibited lower rates of gastrointestinal tract complication ( < 0.001) and myelosuppression ( < 0.001) than intravenous vinorelbine plus cisplatin. 8 spheres plus BAI cisplatin displays good efficacy and well-tolerated safety profiles in locally advanced NSCLC patients with second-line chemotherapy failure.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Vinorelbine; Cisplatin; Quality of Life; Lung Neoplasms; Vinblastine; Antineoplastic Combined Chemotherapy Protocols
PubMed: 33332223
DOI: 10.1089/cbr.2020.4301 -
Anticancer Research Oct 2017To evaluate the efficacy and toxicity of vinorelbine and gemcitabine (NG) versus vinorelbine and cisplatin (NP) in anthracycline- and taxane-pretreated patients with... (Comparative Study)
Comparative Study Randomized Controlled Trial
AIM
To evaluate the efficacy and toxicity of vinorelbine and gemcitabine (NG) versus vinorelbine and cisplatin (NP) in anthracycline- and taxane-pretreated patients with HER2-negative advanced breast cancer.
PATIENTS AND METHODS
Patients were randomly assigned on a 1:1 schedule to receive no more than six cycles of NG or NP. Dosing for the NG group was 25 mg/m vinorelbine and 1,000 mg/m gemcitabine, given on days 1 and 8 every 3 weeks; for the NP group,25 mg/m vinorelbine was given on days 1 and 8, and 75 mg/m cisplatin was given on day 1 every 3 weeks. The primary endpoint was disease control rate (DCR). The secondary endpoints were the progression-free survival (PFS), overall survival (OS) and safety.
RESULTS
The full analysis set comprised of 37 patients receiving NG and 37 receiving NP. The DCR was 70.3% with NG and 64.9% with NP (p=0.619). Median PFS were 7 months (95% CI=5.88-8.12) and 6 months (95% CI=5.29-6.71) respectively in NG and NP group [hazard ratio (HR)=1.696; 95% confidence interval (CI)=0.73-3.93; p=0.217)]. Corresponding median OS was 18 (95% CI=10.35-13.65) months and 12 (95% CI=15.83-20.17) months (HR=1.219; 95% CI=0.67-2.23; p=0.521). For adverse events, neutropenia and nausea/vomiting were milder in the NG group than in the NP group (all p<0.05).
CONCLUSION
Although no significant differences were observed in terms of DCR, PFS and OS, with milder toxicity, NG appeared to be a more valuable first-line treatment regimen than NP in anthracycline- and taxane-pretreated patients with HER2-negative advanced breast cancer.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; China; Cisplatin; Deoxycytidine; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Female; Humans; Kaplan-Meier Estimate; Middle Aged; Receptor, ErbB-2; Time Factors; Treatment Outcome; Vinblastine; Vinorelbine; Gemcitabine
PubMed: 28982882
DOI: 10.21873/anticanres.12000 -
Breast Cancer Research : BCR Feb 2022Clinical cancer imaging focuses on tumor growth rather than metastatic phenotypes. The microtubule-depolymerizing drug, Vinorelbine, reduced the metastatic phenotypes of...
Clinical cancer imaging focuses on tumor growth rather than metastatic phenotypes. The microtubule-depolymerizing drug, Vinorelbine, reduced the metastatic phenotypes of microtentacles, reattachment and tumor cell clustering more than tumor cell viability. Treating mice with Vinorelbine for only 24 h had no significant effect on primary tumor survival, but median metastatic tumor survival was extended from 8 to 30 weeks. Microtentacle inhibition by Vinorelbine was also detectable within 1 h, using tumor cells isolated from blood samples. As few as 11 tumor cells were sufficient to yield 90% power to detect this 1 h Vinorelbine drug response, demonstrating feasibility with the small number of tumor cells available from patient biopsies. This study establishes a proof-of-concept that targeted microtubule disruption can selectively inhibit metastasis and reveals that existing FDA-approved therapies could have anti-metastatic actions that are currently overlooked when focusing exclusively on tumor growth.
Topics: Animals; Breast Neoplasms; Cell Line, Tumor; Female; Humans; Mice; Microtubules; Neoplasm Metastasis; Vinorelbine
PubMed: 35164808
DOI: 10.1186/s13058-022-01506-2 -
Irish Journal of Medical Science Aug 2017Breast carcinoma metastasis to the gastrointestinal tract is rare and more frequently associated with lobular than ductal carcinoma (Borst and Ingold, Surg... (Review)
Review
BACKGROUND
Breast carcinoma metastasis to the gastrointestinal tract is rare and more frequently associated with lobular than ductal carcinoma (Borst and Ingold, Surg 114(4):637-641 [1]). The purpose of this article is to present a case based review of a unique gastrointestinal metastasis and literature review.
METHODS
A 46 year old lady with metastatic invasive ductal breast cancer was admitted to A&E with sudden onset of epigastric and left shoulder pain. She completed the first cycle of capecitabine/vinorelbine 1 week previously. Clinical examination revealed a tender epigastrium with rigidity in the upper abdomen. Free air under the diaphragm and a positive Rigler's sign was radiologically identified. A laparoscopy demonstrated a fibrinous exudate in the left upper quadrant consistent with a walled off lesser curvature gastric perforation. A subsequent oesophagogastroduodenoscopy (OGD) demonstrated a healed gastric ulcer of benign appearance; however the pathology confirmed metastatic breast carcinoma.
RESULTS
Literature review confirmed no previously reported cases of vinorelbine induced gastric perforation. Four cases of metastatic breast cancer with gastric metastasis presenting with perforation were identified; three of these cases (Fra et al., Presse Med 25(26):1215 (1996) [2], Solis-Caxaj et al., Gastroenterol Clin Biol 28(1):91-92 (2004) [3], Ghosn et al., Bull Cancer 78(11):1071-1073 (1991) [4]), were in the French medical literature, including one male patient (Fra et al., Presse Med 25(26):1215 (1996) [2]) and at least one ductal breast carcinoma (Solis-Caxaj et al., Gastroenterol Clin Biol 28(1):91-92 (2004) [3]). The fourth case (van Geel et al., Ned Tijdschr Geneeskd 144(37):1761-1763 (2000) [5]), was in the Dutch medical literature and a lobular breast carcinoma.
CONCLUSION
This case represents a rare complication of breast cancer chemotherapy, the subsequent significant benefit the patient received from treatment is consistent with the chemosensitivity to therapy that also resulted in gastric perforation. Five years after gastric perforation she resumed palliative chemotherapy after progression on sequential hormonal therapies.
Topics: Adult; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Female; Humans; Middle Aged; Stomach Neoplasms; Vinblastine; Vinorelbine
PubMed: 28039597
DOI: 10.1007/s11845-016-1536-1 -
Asia-Pacific Journal of Clinical... Jun 2017Despite recent advances, outcomes for patients with stage III non-small cell lung cancer (NSCLC) with concurrent chemoradiotherapy (CRT) remain poor. We evaluated the...
Concurrent chemoradiation with cisplatin and vinorelbine followed by consolidation with oral vinorelbine in locally advanced non-small cell lung cancer (NSCLC): the phase II CONCAVE study.
AIM
Despite recent advances, outcomes for patients with stage III non-small cell lung cancer (NSCLC) with concurrent chemoradiotherapy (CRT) remain poor. We evaluated the combination of ciplatin/vinorelbine and concurrent thoracic radiotherapy followed by consolidation oral vinorelbine in this phase II study.
METHODS
Eligible patients with unresectable stage III NSCLC received cisplatin intravenous (IV) 40 mg/m and vinorelbine IV 20 mg/m on days 1, 8, 22 and 29 concurrent with thoracic radiotherapy of 60 Gy in 30 fractions. Four to eight weeks later, oral vinorelbine 60 mg/m day 1 and 8 every 3 weeks was given for 3 cycles. The primary end point was overall response rate (ORR). Secondary end points were safety, quality of life, progression-free survival (PFS) and overall survival (OS).
RESULTS
Twenty-seven eligible patients were enrolled from December 2007 to June 2010 before the trial was prematurely closed due to toxicity concerns. The median age was 63 years (range, 42-71), 56% were male, 52% ECOG 0 and 52% stage IIIa. The ORR was 81% (including 37% complete response rate) and disease control rate of 93%. The median PFS was 11 months and median OS was 26 months. Consolidation vinorelbine was associated with significant grade 3/4 toxicity (68%) including grade 3-5 febrile neutropenia (27%) and respiratory infections (36%) including two deaths in the consolidation phase (9%).
CONCLUSIONS
Consolidation oral vinorelbine after CRT was associated with significant toxicity. Overall, this regimen achieved a high ORR and survival results comparable to other CRT protocols but the significant toxicity precludes further evaluation of this approach.
Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Female; Humans; Lung Neoplasms; Male; Middle Aged; Quality of Life; Vinblastine; Vinorelbine
PubMed: 28181415
DOI: 10.1111/ajco.12649 -
The Oncologist Oct 2017VELVET Cohort 1 demonstrated the applicability of pertuzumab, trastuzumab, and vinorelbine as an alternative first-line treatment regimen for patients with HER2-positive...
BACKGROUND
VELVET Cohort 1 demonstrated the applicability of pertuzumab, trastuzumab, and vinorelbine as an alternative first-line treatment regimen for patients with HER2-positive locally advanced or metastatic breast cancer (MBC) who cannot receive docetaxel. Co-infusion of pertuzumab and trastuzumab may reduce clinic time and medical resource utilization. We report results from Cohort 2, in which pertuzumab and trastuzumab were co-infused, followed by vinorelbine.
PATIENTS AND METHODS
During cycle 1, patients with HER2-positive locally advanced or MBC received loading doses of pertuzumab (840 mg) and trastuzumab (8 mg/kg) on consecutive days, followed by vinorelbine (25 mg/m) on days two and nine. From cycle 2 onwards, patients received a co-infusion of pertuzumab (420 mg) and trastuzumab (6 mg/kg) on day one, followed by vinorelbine (30-35 mg/m) on days one and eight (or days two and nine). The primary endpoint was objective response rate (ORR) in patients with measurable disease. Secondary endpoints included progression-free survival (PFS) and safety.
RESULTS
Cohort 2 enrolled 107 patients. The ORR was 63.7% (95% confidence interval [CI] 53.0-73.6) in patients with measurable disease (91/107; 85.0%). Median PFS was 11.5 months (95% CI 10.3-15.8). The most common adverse events [AEs] were diarrhea (57.9%), neutropenia (57.0%), and nausea (41.1%). Grade ≥3 AEs occurred in 85 patients (79.4%) and serious AEs in 44 patients (41.1%). Eighteen patients (16.8%) had AEs suggestive of congestive heart failure.
CONCLUSION
These results support the feasibility of pertuzumab and trastuzumab co-infusion from a safety perspective and support Cohort 1 conclusions that vinorelbine offers an alternative chemotherapy companion for pertuzumab and trastuzumab. 2017;22:1160-1168 IMPLICATIONS FOR PRACTICE: Combined treatment with pertuzumab, trastuzumab, and docetaxel is the standard of care for first-line HER2-positive metastatic breast cancer. However, some patients cannot, or choose not to, receive docetaxel. VELVET Cohort 2 results support the results from Cohort 1 that suggest that pertuzumab plus trastuzumab and vinorelbine is a suitable alternative for these patients. In addition to this, results from Cohort 2 support the feasibility of administering pertuzumab and trastuzumab together in a single infusion bag, which has the potential to offer greater patient convenience and reduce active health care professional time and medical resource utilization compared with administering them separately.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Humans; Trastuzumab; Treatment Outcome; Vinblastine; Vinorelbine
PubMed: 28592618
DOI: 10.1634/theoncologist.2017-0079 -
European Journal of Pharmaceutical... Jan 2021NSCLC is the most common type of lung cancer. However, non-specific contrast agents, radiopharmaceuticals, and treatment methods are insufficient in early diagnosis and...
NSCLC is the most common type of lung cancer. However, non-specific contrast agents, radiopharmaceuticals, and treatment methods are insufficient in early diagnosis and eradication of all tumor tissue. Therefore, the formulation of a novel, targeted, specific theranostic agents possess critical importance. In our previous study, paclitaxel and vinorelbine encapsulating, Tc-99m radiolabeled, folate targeted, nanosized liposomes were formulated and found promising due to characterization properties, high cellular uptake, and cytotoxicity. In this study, in vivo therapeutic and diagnostic efficacy of liposomal formulations were tested by biodistribution study, evaluation of tumor growth inhibition, and histopathologic examination after in vitro assays on LLC1 cells. Both actively and passively targeted liposomal formulations exhibited high cellular uptake, and co-drug encapsulating liposomes showed a greater cytotoxicity profiles than free drug combination in LLC1 cells. By the results of biodistribution studies performed in NSCLC tumor-bearing C57BL/6 mice, the uptake of radiolabeled, actively folate targeted, co-drug encapsulating liposomal formulation was found to be higher in tumor tissue when compared to non-actively targeted one. Also, more effective treatment was achieved by using folate-targeted, co-drug encapsulating liposomal formulation when compared to free drugs combination according to changes in tumor size of mice. Furthermore, liposomal formulations showed lower toxicity compared to free drug combinations in the toxicity study considering body weight. Moreover, according to the histopathological study, folate targeted, co-drug encapsulating liposomes not only inhibited the tumor growth effectively but also restricted the lung metastasis entirely.
Topics: Animals; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Folic Acid; Liposomes; Lung Neoplasms; Mice; Mice, Inbred C57BL; Paclitaxel; Precision Medicine; Tissue Distribution; Vinorelbine
PubMed: 32987115
DOI: 10.1016/j.ejps.2020.105576 -
Theranostics 2019: Tumor angiogenesis promotes tumor development, progression, growth, and metastasis. Metronomic chemotherapy involves the frequent administration of low-dose...
: Tumor angiogenesis promotes tumor development, progression, growth, and metastasis. Metronomic chemotherapy involves the frequent administration of low-dose chemotherapeutic agents to block angiogenic activity and reduce side effects. : MDA-MB-231 cells were treated with various concentrations of artemisinin (ART) and vinorelbine (NVB) and the cytotoxic effects of ART/NVB were determined using the CCK-8 assay. Mitochondrial reactive oxygen species (ROS) levels, mitochondrial membrane potential (∆Ψm) and mass were assessed using MitoSOX, TMRE and MitoTracker green staining. Western blot analysis was used to quantify the expression of autophagy-related proteins. Herein, by using bioinformatics analysis and experimental verification, we identified CREB as a master in MDA-MB-231 cells. : We found that artemisinin (ART), which exhibits anti-angiogenic and anti-cancer effects via mitochondrial regulation, synergized with vinorelbine (NVB) to inhibit MDA-MB-231 cell proliferation. ART and NVB cooperated to regulate mitochondrial biogenesis. CREB acted as a crucial regulator of PGC1α and VEGF, which played critical roles in NVB-dependent growth factor depletion. Moreover, CREB suppression significantly reversed mitochondrial dysfunction following ART/NVB co-treatment. In addition, combination treatment with ART and NVB significantly suppressed tumor growth in a nude mouse xenograft model, with downregulated CREB and PGC1α expression levels observed in tumor biopsies, in agreement with our and data. : These findings support the hypothesis that ART affects cancer and endothelial cells by targeting the auto-paracrine effects of VEGF to suppress mitochondrial biogenesis, angiogenesis, and migration between cancer cells and endothelial cells.
Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Combined Chemotherapy Protocols; Artemisinins; Breast Neoplasms; Cell Line, Tumor; Culture Media, Conditioned; Cyclic AMP Response Element-Binding Protein; Drug Synergism; Endothelium, Vascular; Female; Human Umbilical Vein Endothelial Cells; Humans; Male; Mice, Inbred BALB C; Mitochondria; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Vinorelbine; Xenograft Model Antitumor Assays
PubMed: 31588240
DOI: 10.7150/thno.33353 -
Drug Development and Industrial Pharmacy Jan 2021Gastric cancer is one of the leading causes of cancer-related death worldwide with a poor prognosis. Gastric cancer is usually treated with surgery and chemotherapy,...
Gastric cancer is one of the leading causes of cancer-related death worldwide with a poor prognosis. Gastric cancer is usually treated with surgery and chemotherapy, accompanied by a high rate of metastasis and recurrence. In this paper, R (RRRRRRRR) modified vinorelbine plus schisandrin B liposomes had been successfully constructed for treating gastric cancer. In the liposomes, R was used to enhance the intracellular uptake, schisandrin B was incorporated into liposomes for inhibiting tumor cells metastasis, and vinorelbine was encapsulated into liposomes as antitumor drugs. Studies were performed on BGC-823 cells and were verified in the BGC-823 cell xenografts nude mice . Results demonstrated that the targeting liposomes could induce BGC-823 cells apoptosis, inhibit the metastasis of tumor cells, and increase targeting effects to tumor cells. Meanwhile, action mechanism studies showed that the targeting liposomes could down-regulate VEGF, VE-Cad, HIF-1a, PI3K, MMP-2, and FAK to inhibit tumor metastasis. results exhibited that the targeting liposomes displayed an obvious antitumor efficacy by accumulating selectively in tumor site and induce tumor cell apoptosis. Hence, R modified vinorelbine plus schisandrin B liposomes might provide a safe and efficient therapy strategy for gastric cancer.
Topics: Animals; Apoptosis; Cell Line, Tumor; Cyclooctanes; Lignans; Liposomes; Mice; Mice, Nude; Polycyclic Compounds; Stomach Neoplasms; Vinorelbine
PubMed: 33295825
DOI: 10.1080/03639045.2020.1862169 -
Head & Neck Jan 2018The purpose of this study was to investigate the efficacy and safety of vinorelbine plus cisplatin chemotherapy in patients with recurrent and/or metastatic salivary... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The purpose of this study was to investigate the efficacy and safety of vinorelbine plus cisplatin chemotherapy in patients with recurrent and/or metastatic salivary gland cancer of the head and neck.
METHODS
In this single-arm phase II study, patients with recurrent and/or metastatic salivary gland cancer were treated with i.v. vinorelbine (25 mg/m ) on days 1 and 8 plus cisplatin (80 mg/m ) on day 1 every 3 weeks for 4 or 6 cycles. The primary endpoint was the objective response rate. Progression-free survival (PFS), overall survival (OS), and adverse events were also assessed.
RESULTS
Between September 2008 and November 2014, 40 patients with recurrent and/or metastatic salivary gland cancer received vinorelbine plus cisplatin chemotherapy. The objective response rate was 35.0%, including 1 complete response. Median PFS and OS rates were 6.3 months and 16.9 months, respectively. No treatment-related deaths occurred.
CONCLUSION
Administering vinorelbine plus cisplatin chemotherapy to patients with recurrent and/or metastatic salivary gland cancers is safe and effective.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Republic of Korea; Risk Assessment; Salivary Gland Neoplasms; Single-Blind Method; Survival Analysis; Vinblastine; Vinorelbine
PubMed: 29044862
DOI: 10.1002/hed.24933