Vinorelbine-based Chemotherapy Research Articles

Vinorelbine in Non-Small Cell Lung Cancer: Real-World Data From a Single-Institution Experience.

The use of vinorelbine as a single agent or in combination regimens in non-small cell lung cancer (NSCLC) is associated with satisfactory clinical activity. However, the role of vinorelbine-based chemotherapy in chemonaive locally advanced unresectable or metastatic NSCLC patients, according to real-world treatment patterns, has still not been widely explored. Eighty-one patients treated at a single institution were retrospectively analyzed. Thirty-seven received standard first-line single-agent vinorelbine, and 44 received vinorelbine plus platinum drugs, based on physician’s choice; 61.7% were older than 70 years, and 60.5% were affected by ≥2 comorbidities. Sixty-three patients were evaluable for objective response: 22% achieved partial response and 41% stable disease. Median progression-free survival (PFS) was 5.4 months. A benefit in PFS was observed in patients treated with combinations vs. single-agent vinorelbine (6.7 vs. 3.5 months, p = 0.043). Median overall survival (OS) was 10.4 months without a statistically significant difference between treatments (12.4 vs. 7.5 months). In 55 stage IV patients, OS was positively correlated with combination regimens, M1a stage, or ≤2 metastatic lesions. Grade 3–4 toxicity occurred in 33% of patients, and dose reduction in 11%. A statistically significant higher incidence of toxicity was observed in patients receiving combinations, in women, in patients younger than 75 years, or patients with metastases. In this real-word analysis, we confirmed the efficacy and tolerability of vinorelbine as a single agent or combined with platinums in patients usually underrepresented in controlled clinical trials. Single-agent vinorelbine may represent a suitable option in elderly or unfit NSCLC patients and warrants investigation as a potential drug candidate for immunochemotherapy combination regimens.

Abstract 18: MMP9 inhibition in mouse models of breast cancer: Therapeutic synergy with vinorelbine-based chemotherapy

Abstract The combination of different therapeutic approaches, such as simultaneous targeting of tumor cells and stroma, may be a superior strategy to enhance anti-tumor responses in metastatic breast cancer (BC). Recently, the pro-tumorigenic activity of adipose tissue was further examined and suggested MMP9 promotes BC invasion, angiogenesis, and lung metastasis in mice (Reggiani et al., Cancer Res 2017). In the present work, MMP9 inhibition was combined with distinct therapeutic agents. A monoclonal antibody that inhibits mouse MMP9 was administered to tumor-bearing (4T1) immune-competent BALB/c mice, alone or in combination with low-dose chemotherapy (vinorelbine, V or cyclophosphamide, CTX) or checkpoint inhibitors (anti-PD1 or anti-PDL1 monoclonal antibodies). MMP9 inhibition was also evaluated in diet-induced obese BC mice (Balb/c or FVB background). The anti-tumor response of different combination treatments was assessed by tumor growth measurement, lung metastasis assessment, tumor angiogenesis evaluation through immunofluorescence, and immune system modulation by flow-cytometry. The combination of V and MMP9 inhibition was superior to either agent alone. Tumor growth was reduced in mice administered with combined V and MMP9 inhibition compared to single treatment or control mice, administered with isotype control and saline (41% V+anti-MMP9 vs control, p=0.001). Lung metastases were significantly impaired (37% V+anti-MMP9 vs control, p=0.009). MMP9 inhibition exhibited the greatest reduction in intratumor angiogenesis among therapeutic agents tested (59% vs control, p=0.004). The combination of MMP9 inhibition with V compared to control, reduced B (1%, p=0.008), T cells (2.5%, p=0.01), and macrophages (35%, p=0.05) in the tumor. Inhibiting MMP9 in diet-induced obese BALB/c mice was more effective in reducing tumor growth and metastatic progression, when compared to normal-weight mice (BC volume: 46%, p=0.01; lung metastasis: 53%, p=0.01). These data suggest that the increase of MMP9 release, observed in adipose progenitors when exposed to BC cells (Reggiani et al., Cancer Res 2017), was a mediator of the obesity-dependent pro-tumorigenic activity. Of note, when MMP9 inhibition was initiated in early phases of tumor growth in ErbB2+ BC FVB mice, the reduction of local tumor growth was more pronounced (started at 15 days vs 45 days: 18%, p=0.01; 15 days vs isotype control: 11%, p=0.01; 45 days vs isotype control: 64%, p=0.3 ns). MMP9 inhibition is efficacious in mouse models of BC with concomitant obesity. In human BC patients, response to chemotherapy is reportedly lower, and the risk of relapse is higher in obese sub-population (Ewertz et al., JCO 2011). The additive effects of MMP9 inhibition with V may warrant further studies to characterize underlying molecular mechanisms in BC patients with high body mass index (BMI). Citation Format: Francesca Reggiani, Loredana Vecchi, Valentina Labanca, Patrizia Mancuso, Amanda Mikels-Vigdal, Francesco Bertolini. MMP9 inhibition in mouse models of breast cancer: Therapeutic synergy with vinorelbine-based chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 18.

Vinorelbine-based chemo-radiotherapy in non-small cell lung cancer.

Concomitant radio-chemotherapy improves survival of patients with locally advanced non-small cell lung cancer, with a better local-regional control. We report our experience with vinorelbine-based chemotherapy in neoadjuvant and radical settings in 43 patients. Regimens consisted of cisplatin plus vinorelbine in 74.4% patients and carboplatin plus vinorelbine in 14.0%; 11.6% underwent mono-chemotherapy with oral vinorelbine. We estimated the crude probability of death or local recurrence by the Kaplan-Meier method. Cox regression models were used to identify the main significant predictors of death or local recurrence. A significant effect of the response to treatment was shown on both local disease free-survival (P = 0.004) and overall survival (P <0.0001). Patients with progressive disease after primary treatment had a significantly higher risk of further relapse at both univariate (P = 0.046) and multivariate regression analysis (P = 0.014) than patients with a complete response. They also showed a significantly higher risk of death at both univariate (P = 0.0005) and multivariate regression analysis (P <0.0001) than patients with a complete response. The most common toxicity was hematologic and gastroenteric. We recorded grade III/IV leukopenia in 11%, anemia in 6%, and esophagitis in 14% of the patients. Our experience showed that vinorelbine-based chemotherapy is an effective and safe regimen, in association with a platinum compound and thoracic radiotherapy.

Vinorelbine-based chemotherapy in metastatic epithelioid sarcoma.

e22549Background: Epithelioid sarcoma (ES) is a rare soft tissue sarcoma subtype, with poor and short-term responses to conventional, doxorubicin-based chemotherapy (Jones et al, Am J Clin Oncol 20...

The relationship between polymorphisms of genes regulating DNA repair or cell division and the toxicity of platinum and vinorelbine chemotherapy in advanced NSCLC patients.

Platinum-based chemotherapy and 3rd generation drugs is still the main treatment option for advanced non-small cell lung cancer (NSCLC) patients without activating EGFR mutations or ALK rearrangements. However, the side effects associated with cytostatics are well known. Changes in the genes (e.g. single nucleotide polymorphisms, SNPs) encoding proteins regulating DNA repair or cell division could potentially influence on both the susceptibility of cancer cells to chemotherapy, and the occurrence of toxicities. In presented study, the relationship between the fourteen SNPs in nine DNA repair and cell division regulating genes: ERCC1, XPD, XPA, XPC, XRCC1, XPG, RRM1, BRCA1, STMN1 and the toxicity of first-line chemotherapy in NSCLC patients were investigated. SNPs were determined by SNaPshot PCR® in DNA isolated from peripheral blood of 55 NSCLC patients treated with platinum compound and vinorelbine. The toxicity of therapy was evaluated according to the Common Toxicity Criteria (CTC) Version 4.03. The odds ratio (OR) of severe haematological toxicity was significantly lower in carriers of the T allele of XRCC1 gene (1196A > G, OR = 0.22, 95 % CI: 0.06-0.82, p = 0.018) and higher in the carriers of the T allele (2704C > A) of XPC gene (OR: 7.50, 95 % CI: 0.89-63.17, p = 0.036) compared to the remaining patients. Risk of severe hepatotoxicity was significantly lower in carriers of the C allele of STMN1 (-2166T > C, OR = 0.09, 95 % CI: 0.01-1.12, p = 0.025) than in patients with T allele of this gene. In carriers of G allele (2251A > C, OR: 0.24, 95 % CI: 0.07-0.81, p = 0.017) and T (934G > A, OR: 0.26, 95 % CI: 0.07-0.90, p = 0.029) of XPD gene, risk of severe nephrotoxicity was significantly lower than in other patients. Selected SNPs of genes encoding DNA repair enzymes and cell division regulation proteins could be useful biomarkers for prediction of platinum and vinorelbine-based chemotherapy toxicity in patients with advanced NSCLC.

Setting the Bar for Therapeutic Trials in Non–Small-Cell Lung Cancer: How Low Can We Go?

Setting the Bar for Therapeutic Trials in Non–Small-Cell Lung Cancer: How Low Can We Go?

High expression levels of class III β-tubulin in resected non-small cell lung cancer patients are predictive of improved patient survival after vinorelbine-based adjuvant chemotherapy

The aim of the present study was to determine the frequency and predictive value of the expression of tumor microtubule components in patients with resected non-small cell lung cancer (R-NSCLC) subsequently treated with vinorelbine-based adjuvant chemotherapy. The expression of the microtubule components was evaluated in 85 R-NSCLC tumor samples using immunohistochemistry. All patients received vinorelbine-based chemotherapy. The predictive value of microtubule protein expression for disease-free survival (DFS) and overall survival (OS) was assessed. The expression of the microtubule components was not associated with any baseline clinicopathological factors in the R-NSCLC patients. High tumor expression levels of class III β-tubulin were correlated with an improved DFS (P=0.033) and a trend towards a longer OS (P=0.226). Class II and IV β-tubulins were not correlated with patient outcome. Multivariate analysis of factors, including gender, age, histology, stage and class II, III and IV β-tubulin expression demonstrated that high levels of class III β-tubulin expression were correlated independently with DFS (P= 0.031). These findings suggest that high class III β-tubulin expression levels in resected tumors are predictive of improved DFS in R-NSCLC patients receiving vinorelbine-based chemotherapy.

A Systematic Review of Vinorelbine for the Treatment of Breast Cancer

The purpose of this study was to investigate the efficacy and safety profile of vinorelbine-based chemotherapy in different settings for the treatment of breast cancer. We performed a computerized search using combinations of the following keywords: "breast cancer", "breast neoplasms", "trial", "vinorelbine" and "navelbine". A total of 20 trials were included in this analysis, with a total of 5,080 patients accrued. Taxane was associated with enhanced overall survival (OS; p=0.027) and response rate (RR; p=0.037) as compared with vinorelbine in monotherapy, but did not show significantly favored progression-free survival (PFS; p=0.136). Vinorelbine alone was equivalent to fluoropyrimidine treatment in RR (p=0.79) for the treatment of metastatic breast cancer. For vinorelbine-combined regimens, the analysis showed that the vinorelbine group gave similar results as other regimens for OS (p=0.849) and PFS (p=0.143). The RR of vinorelbine-combined regimens was slightly better than that of the other regimens (OR, 1.17), but the difference was not statistically significant. In neoadjuvant setting, vinorelbine treatment was as active as AC (doxorubicin, cyclophosphamide) or DAC (doxorubicin, cyclophosphamide, docetaxel) regimens with respect to RR (p=0.76) and pathologic complete response (pCR; p=0.77), but showed lower occurrence of grade 3/4 adverse effects. The analysis also demonstrated that vinorelbine-containing therapy is effective as adjuvant, front-line or salvage therapy of metastatic breast cancer, even for patients who were previously treated with anthracyclines or taxanes.

Evaluation of vinorelbine-based chemotherapy as the second or further-line treatment in patients with metastatic breast cancer

Aim of the studyThe study examined the response rate, response duration and toxicity of vinorelbine and fluorouracil or vinorelbine alone in pretreated metastatic breast cancer.Material and methodsBetween June 2001 and September 2009, a group of 103 patients with locally advanced or metastatic breast cancer, who had progressed after anthracycline/taxane chemotherapy, was treated with a vinorelbine-based regimen. The treatment consisted of vinorelbine 25 mg/m2 and 5-fluorouracil (5-FU) 500 mg/m2 administered intravenously on days 1 and 8 of each cycle (53 patients) or vinorelbine alone at a dose of 30 mg/m2 on day 1 and 8 of the cycle, every 3 weeks (50 patients). Patients received chemotherapy as a second or further line of therapy. Treatment was continued until disease progression or unacceptable toxicity. The median age of patients treated with vinorelbine with 5FU was 54 years (range 38–76), and 55.5 years (range 38–73) in the group receiving vinorelbine monotherapy. A total of 417 cycles of chemotherapy were administered – 177 cycles of vinorelbine with 5-FU and 137 cycles of vinorelbine monotherapy. Patients were treated for a median of 4 cycles (range: 1 to 11 cycles). The evaluation of treatment effect was possible in 93 patients (10 patients received only one treatment cycle).ResultsThe overall response rate (ORR) was 17% (7), including 2 (4%) complete responses (CR) and 5 (10.5%) partial responses (PR). Stable disease (SD) was observed in 50% of patients receiving vinorelbine with 5-FU (24 patients). In a group receiving vinorelbine alone the ORR was 20% (9), including 9 PR (20%) and 16 SD (35.5%). The median time to progression (TTP) for the entire group was 18 weeks (95% CI), 22 weeks among patients treated with vinorelbine with 5-FU and 16 weeks for a second group. The most common hematologic adverse events were neutropenia (20% of cycles) and thrombocytopenia (4%), with grade 3/4 incidence of 8% and 1.5% [according to National Cancer Institute Common Toxicity Criteria (NCI CTC)]. Nausea and vomiting were the most frequent non-hematologic forms of toxicity, occurring in 13% of cycles. The doses of cytotoxics were reduced in 26 (25%) cases. There were no treatment-related deaths.ConclusionsVinorelbine alone or in combination with 5-FU is an effective and safe treatment for pretreated advanced/ metastatic breast cancer patients. The combination of vinorelbine with 5-FU appears to be a more efficacious regimen than vinorelbine alone.

Prediction of survival benefits from progression-free survival benefits in advanced non-small-cell lung cancer: evidence from a meta-analysis of 2334 patients from 5 randomised trials

ObjectivesTo investigate whether progression-free survival (PFS) can be considered a surrogate endpoint for overall survival (OS) in advanced non-small-cell lung cancer (NSCLC).DesignMeta-analysis of individual patient data from randomised trials.SettingFive randomised...

Treatment Effect of Neoadjuvant Chemoradiation Therapy for Non-small Cell Lung Cancer Evaluated by Multimodality Imaging and Histopathological Analyses

Purpose/Objective(s): To assess treatment effect of neoadjuvant chemoradiation therapy (NACRT) for locally advanced non-small cell lung cancer (LA-NSCLC) by multi-modality imaging and histopathological diagnosis including molecular biological analyses. Materials/Methods: We retrospectively reviewed the radiation oncology and histopathological records of 11 patients who underwent NACRT for LA-NSCLC and contrast enhanced computed tomography (CECT), magnetic resonance imaging (MRI), and positron emission tomography CT before and after NACRT between 2007 and 2010. There were 10 males and 1 female with a median age of 68 years (range, 54 to 76). Eight had squamous cell carcinomas, one had large cell carcinoma, one had adenocarcinoma, and one was unclassified. NACRT consisted of 2 cycles of cisplatin and vinorelbine-based chemotherapy given concurrently with 3D conformal radiation therapy of 40 Gy in 20 fractions within 4 weeks. Changes of tumor findings on imaging were compared with histopathological diagnosis including molecular biological analyses using immunostaining technique of the surgical specimens. Results: Histopathological manifestation of the Hematoxylin-Eosin stained surgical specimens showed Effect 3 (Ef. 3: no viable tumor cells) in 6 and Effect 2 (Ef. 2: small amount of remnant viable tumor cells) in 5, and negative surgical margin was observed in all cases. Positive ratios of growing cell in remnant viable tumor cells of Ef. 2 cases were less than 15% and positive ratios of double strand breaks were more than 50%. Mean reduction ratio of tumor size on CECT in cases of Ef. 2 and EF. 3 were 38% and 55%. Mean reduction ratios of SUV in cases of Ef. 2 and EF. 3 were 56% and 83%. One case with EF. 3 showed persistent Ffluorodeoxy glucose accumulation at margin of tumor due to inflammatory cells infiltration around necrosis. Signal intensity changes of tumor on diffusion weighted images of MRI did not correlate with histopathological treatment effect. Conclusions: High reduction ratio of tumor size and SUV tended to correlate with good histopathological treatment effect of NACRT for NSCLC. Even if the remnant viable tumor cells were present morphologically in the surgical specimens, more than 50% of them had double strand breaks of DNA and growing cell ratios were less than 15%. Author Disclosure: H. Ikushima: None. K. Kondo: None. Y. Otomi: None. H. Maezawa: None.

Vinorelbine-Based Chemo-Radiotherapy in Non-Small Cell Lung Cancer

Concomitant radio-chemotherapy improves survival of patients with locally advanced non-small cell lung cancer, with a better local-regional control. We report our experience with vinorelbine-based chemotherapy in neoadjuvant and radical settings in 43 patients. Regimens consisted of cisplatin plus vinorelbine in 74.4% patients and carboplatin plus vinorelbine in 14.0%; 11.6% underwent mono-chemotherapy with oral vinorelbine. We estimated the crude probability of death or local recurrence by the Kaplan-Meier method. Cox regression models were used to identify the main significant predictors of death or local recurrence. A significant effect of the response to treatment was shown on both local disease free-survival (P = 0.004) and overall survival (P <0.0001). Patients with progressive disease after primary treatment had a significantly higher risk of further relapse at both univariate (P = 0.046) and multivariate regression analysis (P = 0.014) than patients with a complete response. They also showed a significantly higher risk of death at both univariate (P = 0.0005) and multivariate regression analysis (P <0.0001) than patients with a complete response. The most common toxicity was hematologic and gastroenteric. We recorded grade III/IV leukopenia in 11%, anemia in 6%, and esophagitis in 14% of the patients. Our experience showed that vinorelbine-based chemotherapy is an effective and safe regimen, in association with a platinum compound and thoracic radiotherapy.

Customising chemotherapy in advanced nonsmall cell lung cancer: daily practice and perspectives

Treating patients with advanced nonsmall cell lung cancer (NSCLC) is a daunting task but during recent years new options have emerged. By tailoring treatment using either information on histological subtypes of NSCLC or biomarkers it is now possible to improve outcome and maintain stable quality of life. We conducted a literature search of tailored treatment already implemented in advanced NSCLC in order to highlight the information required to decide on the optimal oncological treatment for individual patients. 16 studies were identified by literature review. Significantly improved outcome was demonstrated in patients with nonsquamous NSCLC treated with cisplatin/pemetrexed in pre-planned, exploratory and retrospective analysis from large-scale, randomised trials. Level 1 evidence showed significantly better progression-free survival when patients carrying an epidermal growth factor receptor (EGFR) mutation were treated with gefitinib compared to standard chemotherapy. Retrospective, unplanned analysis of excision repair cross complementation group 1 (ERCC1) and betatubulin III upregulation demonstrated poorer outcome in NSCLC patients treated with platinum-doublets and vinorelbine-based chemotherapy, respectively. In conclusion, tailoring treatment according to either histological subtype or EGFR mutation status in advanced NSCLC should today be part of daily practice based on current evidence. Future biomarkers need optimisation of methodology and prospective validation before clinical implementation.

474 First results of an international, retrospective observational study of metastatic breast cancer patients treated with oral vinorelbine based-chemotherapy

474 First results of an international, retrospective observational study of metastatic breast cancer patients treated with oral vinorelbine based-chemotherapy

MDR1 Single Nucleotide Polymorphisms Predict Response to Vinorelbine-Based Chemotherapy in Patients with Non-Small Cell Lung Cancer

Background: The polymorphisms of genes participate in metabolism and transport, and therefore may have an impact on the response to vinorelbine. Objectives: To investigate whether genotypes of CYP3A5, MDR1 and cyclooxygenase-2 (COX-2) are associated with the response to vinorelbine in non-small cell lung cancers (NSCLC). Methods: We determined the genotypes of CYP3A5(*3), MDR1 (2677G→T at exon 21 and 3435C→T at exon 26 and their haplotypes) and COX-2 (–1195G→A) polymorphisms by PCR-RFLP and chemotherapy response in 69 Chinese Han patients with NSCLC who received a combination chemotherapy of vinorelbine-cisplatin (VC). The χ² test was used to investigate potential associations between genotypes and response to chemotherapy. Odds ratios and 95% confidence intervals were calculated. Results: The 3435 CC genotype was associated with a significantly better chemotherapy response compared with the combined 3435 CT and TT genotypes (p = 0.025). The 2677 GG genotype was also associated with a better chemotherapy response compared with the combined 2677 GT and TT genotype, although it was not statistically significant. Moreover, we analyzed the haplotypes of MDR1 3435-2677: patients harboring the 2677G-3435C haplotype had a statistically significantly better response to chemotherapy compared with those with the other haplotypes combined (p = 0.015). CYP3A5*3 is not likely to correlate with sensitivity to vinorelbine in NSCLC. COX-2 (–1195G) is likely to result in a better response to vinorelbine (nonsignificant). Conclusions: Our findings suggest that MDR1 2677G→T/A and 3435C→T polymorphisms can be used to predict treatment response to VC chemotherapy in NSCLC patients.

MAP4/OP18 mRNA expression predicts progression in patients treated with vinorelbine plus carbolpatin in advanced lung cancer patients in a Multicenter trial

14088 Background: Non-small-cell lung cancer patients with locally advanced or metastatic disease at the time of diagnosis show marginal response to chemotherapy in terms of tumor shrinkage, time to progression and median survival. MAP4 and stahmin have been previously reported as potential markers of resistance to treatment based on microtubule-destabilizing agents. Methods: In this multicenter study, we have used quantitative PCR to analyse expression of MAP4, stathmin, beta-tubulin III, BRCA1 and ERCC1 in mRNA isolated from peripheral blood samples of 51 non-small-cell lung cancer patients treated with vinorelbine/carboplatin. Results: In a preliminary set, 29 patients with stage IIIB and IV were analyzed. Lower levels of MAP4/OP18 mRNA expression are statistically related with response to vinorelbine-based treatment (p=0,029). This significant relationship is maintained in a second analysis after third cycle of treatment (p=0,032). Higher levels of MAP4/op18 were associated with a lower TTP (p=0,05). Conclusions: Our preliminary results suggest that the ratio MAP4/OP18 may be a good predictor of response for patients with non-small-cell lung cancer treated with vinorelbine-based chemotherapy. No significant financial relationships to disclose.

CYP450 polymorphisms predict clinic outcomes to vinorelbine-based chemotherapy in patients with non-small-cell lung cancer

CYP2C19*2(G681A), CYP2C19*3(G636A), CYP2D6*4(C188T), CYP2D6*2(C2938T, G4268C), CYP3AP1*3- G44A and CYP3A5*3(A22893G) are the most common polymorphisms detected among Chinese that may influence the efficacy of vinorelbine-based therapies to treat non-small-cell lung cancer (NSCLC). We detected the genotypes of these polymorphisms by PCR-RFLP in 59 patients with NSCLC and assessed their responses to vinorelbine. CYP2D6*4(C188T), CYP3AP1*3 (G -44 A) and CYP3A5*3 were found to be associated with response to vinorelbine. For the 2D6*4 polymorphism, the 18 of 32 (56.25%) patients with homozygous (C/C) responded to this therapy, while 6 of 27 (22.22%) of those heterozygous (C/T) at this site responded. (χ2=5.68, p < 0.05) For the 3AP1*1/*3 polymorphism, 12 of 42 (28.57%) patients with homozygous (A/A) responded, while 12 of 17 (70.59%) with heterozygous (A/G) and homozygous (G/G) responded (χ2=7.19, p < 0.01). CYP3A5*3 polymorphism has a result corresponding to 3AP1*3 polymorphism. Other polymorphisms were not associated with response to vinorelbine. No significant difference in toxicity and survival was observed according to SNP genotype.

Vinorelbine‐based salvage chemotherapy for therapy‐refractory aggressive leukaemias

This study examined the ability of the semi-synthetic vinca alkaloid, Vinorelbine/Navelbine, to cause apoptotic death in freshly obtained primary leukaemia cells from 53 patients with haematological malignancies, including 22 patients with acute lymphoblastic leukaemia (ALL), 24 patients with chronic lymphocytic leukaemia (CLL), three patients with chronic myeloid leukaemia in blast crisis (CML-BC) and four patients with acute myeloid leukaemia (AML). Vinorelbine caused apoptosis in primary leukaemia cells from 42 (79%) of these leukaemia patients. Objective responses, including complete remission (CR) and CR with incomplete haematological recovery, were achieved in 12 of 17 (71%) patients with aggressive and therapy-refractory leukaemias, including five of nine patients with relapsed ALL, three of three patients with CML-BC and four of five patients with rapidly progressive CLL, who were treated with a vinorelbine-based salvage chemotherapy regimen. Drug sensitivity profiling of multidrug-resistant primary cancer cells using apoptosis assays revealed a significant association between Vinorelbine sensitivity in vitro and the likelihood of an objective clinical response to Vinorelbine-based chemotherapy. Vinorelbine-sensitivity testing of primary leukaemia cells might help tailor Vinorelbine-based salvage regimens to those patients who are most likely to respond.

Expression of Class III β-Tubulin Is Predictive of Patient Outcome in Patients with Non–Small Cell Lung Cancer Receiving Vinorelbine-Based Chemotherapy

To determine the prevalence and the prognostic value of microtubule component expression in tumors of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). Expression of microtubular components was immunohistochemically examined in 93 tumor samples from untreated patients with stage III and IV NSCLC. All patients received vinorelbine-based chemotherapy. Response to chemotherapy, progression-free survival, and overall survival were correlated with the expression of microtubule proteins. The response rate was 27.3% (21 partial responses among 77 valuable patients). Although expression of microtubule components was not associated with the response rate, high class III beta-tubulin expression was correlated with resistance to vinorelbine, defined as disease progression under treatment. Patients whose tumors expressed high levels of class III beta-tubulin isotype had shorter progression-free survival and overall survival (P = 0.002 and 0.001, respectively). High Delta2 alpha-tubulin expression was associated with a shorter overall survival (P = 0.018). Tubulin II levels were not found to be correlated with patient outcome. A multivariate analysis, taking into account sex, age, histology, stage, weight loss, and class II beta-tubulin, class III beta-tubulin, and Delta2 alpha-tubulin levels, confirmed that class III beta-tubulin expression was independently correlated with progression-free survival (P = 0.04) and overall survival (P = 0.012). These findings suggest that a high level of expression of class III beta-tubulin in tumor cells is associated with resistance to vinorelbine and a poor prognosis in patients with NSCLC receiving vinorelbine-based chemotherapy.

P-479 Expression of class III beta tubulin is predictive of patientoutcome in patients with non-small cell lung cancer receiving vinorelbine-based chemotherapy

P-479 Expression of class III beta tubulin is predictive of patientoutcome in patients with non-small cell lung cancer receiving vinorelbine-based chemotherapy