vinflunine and Breast-Neoplasms

Breast cancer is the most frequently diagnosed cancer and the highest cause of cancer mortality in females worldwide. The development of drugs improving overall survival in late-stage metastatic breast cancer remains a challenge. Vinflunine is the most recently developed drug in the vinca alkaloid class. Its arrival has been eagerly awaited for treatment of solid tumors, and in particular, for metastatic breast cancer.. The pharmacological features of vinflunine are described. Its clinical development as monotherapy or in combination in metastatic breast cancer is detailed. A literature search on the topic was conducted through PubMed, clinical trials and the proceedings of the main cancer congresses.. The overall results from phase III studies, and in particular those that combined vinflunine with capecitabine, have been less favorable. The combination's effectiveness was at best moderate compared with other drugs which also target metastatic breast cancer, and complicated by significant hematological and gastrointestinal adverse effects. Its use in advanced metastatic breast cancer cannot currently be recommended.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Capecitabine; Female; Humans; Vinblastine

Vinflunine is a novel microtubule inhibitor of the vinca alkaloid class currently in development for the treatment of advanced transitional cell carcinoma of the urothelium (TCCU) and other solid tumors. This review summarizes the clinical activity of vinflunine as a single agent or in combination with other antineoplastic drugs. Vinflunine is active against a variety of tumor types, including advanced TCCU, metastatic breast cancer, advanced non-small cell lung cancer, and malignant pleural mesothelioma. It has a manageable and noncumulative toxicity profile, and its specific mechanism of action has been linked to a reduced potential for peripheral sensory neuropathy. The activity and tolerability of this agent warrant further investigation. Phase 3 trials are underway to further define the extent of clinical benefit provided by vinflunine in patients with advanced solid malignancies.

Topics: Animals; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Carcinoma, Transitional Cell; Clinical Trials as Topic; Humans; Mesothelioma; Mice; Pleural Neoplasms; Tubulin Modulators; Urinary Bladder Neoplasms; Urothelium; Vinblastine

Vinflunine (Javlor) is the first fluorinated microtubule inhibitor belonging to the Vinca alkaloids family. Vinflunine is obtained by semisynthesis using superacidic chemistry to selectively introduce two fluorine atoms at the 20' position of the catharanthine moiety. This compound has been selected for clinical development on the basis of encouraging preclinical activity that warrants study in patients with a wide spectrum of solid tumors. Clinically significant activity has been seen in phase II studies, mainly in the treatment of transitional cell carcinoma of the urothelial tract, non-small cell lung cancer, and carcinoma of the breast. Vinflunine is currently in phase III trial assessment in patients with (second line) transitional cell carcinoma of the urothelium and first-line advanced breast cancer. The efficacy of vinflunine in patients with advanced non-small cell lung cancer previously treated with a platinum-containing regimen was confirmed by a large phase III trial.

Topics: Animals; Breast Neoplasms; Carcinoma; Carcinoma, Transitional Cell; Clinical Trials as Topic; Drug Evaluation, Preclinical; Humans; Lung Neoplasms; Models, Biological; Neoplasms; Treatment Outcome; Tubulin Modulators; Urologic Neoplasms; Urothelium; Vinblastine

Despite the recent trend toward treatment of early stage breast cancer aggressively with anthracyclines and taxanes, nearly half of those women will have metastatic recurrence. Moreover, because of the increasing prior exposure to these drugs, far more women facing first-line therapy for recurrent disease will now have developed anthracycline- and taxane-refractory metastatic breast cancer (ATRMBC), presenting a major therapeutic challenge. A number of established drugs are showing promise in this setting: capecitabine alone or combined with lapatinib; gemcitabine; vinorelbine; and oxaliplatin. At the same time, a variety of new drugs are emerging for potential use in ATRMBC. Among the drugs in clinical development that have shown promising activity include novel classes of compounds (camptothecins and epothilones), newer members of established classes (pemetrexed and vinflunine), and agents with novel mechanisms of action (the mitosis inhibitor E7389 and the ascidian-derived anticancer compound trabectedin). Several molecularly targeted agents are also being evaluated in ATRMBC, including interleukin-2 receptor-binding denileukin diftitox, and 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), which inhibits the protein chaperone heat shock protein 90.

Topics: Antineoplastic Agents; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Camptothecin; Clinical Trials as Topic; Deoxycytidine; Dioxoles; Diphtheria Toxin; Drug Resistance, Neoplasm; Drugs, Investigational; Epothilones; Female; Furans; Gemcitabine; Glutamates; Guanine; Humans; Interleukin-2; Ketones; Lapatinib; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Pemetrexed; Quinazolines; Recombinant Fusion Proteins; Tetrahydroisoquinolines; Trabectedin; Vinblastine; Vinorelbine

Systemic therapy for breast cancer is undergoing many interesting advances. In recent years, a better understanding of the underlying biology of cancer has led to the identification of several opportunities to target cellular pathways for therapeutic advantage. Hormonal therapy is often chosen as the first line of therapy because it is generally very well tolerated. However, most patients eventually become unresponsive to endocrine manipulation. Improved understanding of the mechanisms of hormonal resistance, and of the interplay between hormone receptors and cellular growth pathways, provides the rationale for combining signal transduction inhibitors and hormonal agents to overcome resistance. Emerging data from preclinical studies suggest that this goal might be achievable in the clinic. Antiangiogenic therapy has shown efficacy in colorectal and lung cancer and appears promising in breast cancer, although improved overall survival has not yet been shown. There have also been advances in cytotoxic chemotherapy. Reformulation of paclitaxel in polyoxy-castor-oil-free albumin nanoparticles (ABI-007) has allowed more convenient, safer, and enhanced drug delivery with associated improvement in outcomes. New agents with novel mechanisms of action are also in development and appear to have activity in cancer cells that are resistant to currently available agents.

Topics: Angiogenesis Inhibitors; Aromatase Inhibitors; Breast Neoplasms; ErbB Receptors; Estradiol; Female; Fulvestrant; Humans; MAP Kinase Signaling System; Paclitaxel; Sirolimus; Vinblastine

Capecitabine is an approved standard therapy for anthracycline- and taxane-pretreated locally advanced or metastatic breast cancer (BC). Vinflunine has demonstrated single-agent activity in phase II studies in this setting and activity and tolerability when combined with capecitabine. We compared the combination of vinflunine plus capecitabine (VC) with single-agent capecitabine.. Patients with locally recurrent/metastatic BC previously treated or resistant to an anthracycline and resistant to taxane therapy were randomly assigned to either vinflunine (280 mg/m2, day 1) plus oral capecitabine [825 mg/m2 twice daily (b.i.d.), days 1-14] every 3 weeks (q3w) or single-agent oral capecitabine (1250 mg/m2 b.i.d., days 1-14) q3w. The primary end point was progression-free survival (PFS) assessed by an independent review committee. The study had 90% power to detect a 30% improvement in PFS.. Overall, 770 patients were randomised. PFS was significantly longer with VC than with capecitabine alone [hazard ratio, 0.84, 95% confidence interval (CI), 0.71-0.99; log-rank P = 0.043; median 5.6 versus 4.3 months, respectively]. Median overall survival was 13.9 versus 11.7 months with VC versus capecitabine alone, respectively (hazard ratio, 0.98; 95% CI, 0.83-1.15; log-rank P = 0.77). No difference in quality of life was observed between the two treatment arms. The most common adverse events (NCI CTCAE version 3.0) in the combination arm were haematological and gastrointestinal. Grade 4 neutropenia was more frequent with VC (12% versus 1% with capecitabine alone); febrile neutropenia occurred in 2% versus 0.5%, respectively. Hand-foot syndrome was less frequent with VC (grade 3: 4% versus 19% for capecitabine alone). Peripheral neuropathy was uncommon in both arms (grade 3: 1% versus 0.3%).. Vinflunine combined with capecitabine demonstrated a modest improvement in PFS and an acceptable safety profile compared with capecitabine alone in patients with anthracycline- and taxane-pretreated locally recurrent/metastatic BC.. NCT01095003.

Topics: Adult; Aged; Aged, 80 and over; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Capecitabine; Chemotherapy-Induced Febrile Neutropenia; Drug Resistance, Neoplasm; Female; Hand-Foot Syndrome; Humans; Middle Aged; Neoplasm Recurrence, Local; Neurotoxicity Syndromes; Peripheral Nervous System Diseases; Progression-Free Survival; Quality of Life; Survival Analysis; Taxoids; Vinblastine

There is no standard treatment after progression on second-line chemotherapy for metastatic breast cancer (MBC). We compared vinflunine with physician's choice of alkylating agent (AA) for patients with heavily pretreated MBC.. In this open-label phase III trial, patients with MBC were included if they had received at least two prior chemotherapy regimens for MBC and had received anthracycline, taxane, antimetabolite and vinca alkaloid therapy. Patients were no longer candidates for these chemotherapies because of resistance and/or intolerance. Patients were randomised to either vinflunine 280 mg/m2 intravenously every 3 weeks (q3w) or AA monotherapy q3w. Stratification factors were performance status, number of prior chemotherapy lines for MBC, disease measurability and study site. The primary end point was overall survival (OS).. A total of 594 patients were randomised (298 to vinflunine, 296 to AA). There was no difference between treatment arms in OS (hazard ratio 1.04, P = 0.67; median 9.1 months for vinflunine versus 9.3 months for AA), progression-free survival (hazard ratio 0.94, P = 0.49; median 2.5 versus 1.9 months, respectively) or overall response rate (6% versus 4%, respectively). However, the disease control rate was significantly higher with vinflunine than AA (44% versus 35%, respectively; P = 0.04). The most common adverse events (any grade) were haematological and gastrointestinal disorders and asthenia in both arms. The most common grade 3/4 adverse events were neutropenia (19% versus 11% with vinflunine versus AA, respectively) and asthenia (10% versus 4%).. Vinflunine 280 mg/m2 q3w did not improve OS compared with the physician's choice of AA as third- or later-line therapy for MBC. Vinflunine demonstrated an acceptable safety profile, suggesting that vinflunine 320 mg/m2 merits evaluation.. NCT01091168.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Female; Humans; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Quality of Life; Survival Analysis; Treatment Outcome; Vinblastine

Vinflunine (VFL) is a bifluorinated tubulin-targeted agent of the vinca alkaloids class active in advanced stage breast cancer. We conducted a phase I study combining VFL with epirubicin (EPR) to establish the recommended dose (RD), to evaluate the safety and efficacy profiles and to investigate potential pharmacokinetic (PK) drug-drug interaction (DDI).. Two schedules (day 1 every 3 weeks; days 1 and 8 every 3 weeks) were investigated as first-line chemotherapy of metastatic breast cancer patient. PK DDI was evaluated through population PK approaches.. Thirty-nine patients received a total of 197 cycles of the VFL-EPR combination (median 6). The RDs were VFL 250 mg/m(2) + EPR 75 mg/m(2) every 3 weeks for schedule 1 and VFL 170 mg/m(2) + EPR 35 mg/m(2) every 3 weeks for schedule 2. The PK analysis demonstrated no clinically relevant mutual DDI between VFL and EPR. The main dose-limiting toxicity was neutropenia. The most frequent non-haematological adverse events were nausea, fatigue, constipation, vomiting, anorexia and stomatitis. Objective response rate was achieved in 45.9 % of the patients.. VFL-EPR combination is feasible with manageable toxicity. The antitumour activity was promising and supports further evaluation.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Epirubicin; Female; Humans; Maximum Tolerated Dose; Middle Aged; Neoplasm Metastasis; Vinblastine; Young Adult

This open label phase II study evaluated the safety and efficacy of vinflunine in patients with breast cancer previously treated with a vinorelbine-based regimen and who progressed during or within 6 months of completing this chemotherapy.. Thirty eight patients received vinflunine 320 mg/m(2) once every 3 weeks. The primary efficacy endpoint was overall response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety.. ORR was 8.3% (95% CI: 1.75-22.4) and DCR was 75% (95% CI: 57.8-87.9). PFS was 4.0 months (95% CI: 2.5-6.1) and OS was 13.6 months (95% CI: 8.7-18.9). Toxicities not hampering dose intensity were as expected neutropenia (75.6% of patients), fatigue (44.7%), constipation (28.9%) and abdominal pain (26.3%).. Vinflunine demonstrated antitumour activity and can be safely administered in breast cancer patients refractory/resistant to vinorelbine.

Topics: Adult; Aged; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Disease-Free Survival; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Middle Aged; Prospective Studies; Survival Rate; Treatment Failure; Treatment Outcome; Vinblastine; Vinorelbine

A phase I study was performed to determine the maximal tolerated dose (MTD), recommended dose (RD), safety and efficacy of vinflunine when combined with capecitabine in patients with metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes, with pharmacokinetic blood sampling to test potential drug-drug interactions.. Sixteen patients with MBC who had received anthracyclines and taxanes in the neo/adjuvant setting, if progression occurred during or within 12 months of chemotherapy completion, and/or as first-line chemotherapy of MBC were enrolled. Vinflunine (VFL) was given on day 1 with capecitabine (CAPE) twice daily from days 1 to 14, every 3 weeks. Three dose levels (DL) were investigated (DL1: VFL 280 mg/m² and CAPE 1,650 mg/m²/day, DL2: VFL 320 mg/m² and CAPE 1,650 mg/m²/day and DL3: VFL 280 mg/m² and CAPE 2,000 mg/m²/day).. The RD was established as vinflunine 280 mg/m² on day 1 plus capecitabine 1,650 mg/m²/day on days 1 to 14 given every 3 weeks. Dose-limiting toxicities were grade 4 neutropenia lasting at least 7 days for 2 patients, anorexia with fatigue for 1 patient and diarrhoea with fatigue, anorexia and febrile neutropenia for 1 patient. Neutropenia was the main toxicity of the combination, it was reported in 15 patients (93.8%) with grade 3 in 7 patients (43.8%) and 22.6% of cycles and grade 4 in 7 patients (43.8%) and 19.8% of cycles. Complications were rare with only one patient experiencing febrile neutropenia at DL exceeding the RD. The most frequent non-haematological toxicities were fatigue and gastrointestinal disorders; however, no grade 3 or 4 episode was observed at the RD. Hand-foot syndrome was reported in 5 patients (31.3%) and 22.6% of cycles, no episode of grade 3 was seen. Concerning pharmacokinetics, no modifications were detected for VFL, while slight accumulation between days 1 and 14 was observed for 5-FU formed from CAPE. The risk of clinical significant drug-drug interaction was considered weak. Objective partial responses were reported in 7 patients, yielding a response rate of 43.8% in the all-treated population according to the investigator assessment.. The combination of vinflunine and capecitabine is safe and showed promising antitumour activity in MBC patients who have failed prior anthracyclines and taxanes. Further clinical development of this combination is warranted.

Topics: Adult; Aged; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Capecitabine; Deoxycytidine; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Drug Synergism; Female; Fluorouracil; Humans; Maximum Tolerated Dose; Middle Aged; Neoplasm Metastasis; Taxoids; Treatment Outcome; Vinblastine

To determine the recommended dose (RD) of vinflunine in combination with trastuzumab in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) and to investigate potential pharmacokinetic (PK) interactions.. In the first part of the study, two dose levels of vinflunine given every 3 weeks were explored (280 and 320 mg/m(2)) combined with trastuzumab (4 mg/kg loading dose and 2 mg/kg weekly). For each level of dose, six patients were enrolled to determine the RD for phase 2 studies (RP2S). In the second part of the study, 18 additional patients at RP2S have been evaluated to confirm safety and investigate preliminary antitumor activity.. The RD was 320 mg/m(2) according to the dose escalation plan. Eleven of 15 additional patients who received this dose experienced dose-limiting toxicities, leading to a reduction in the RD to 280 mg/m(2). When compared to prior trials when vinflunine was used as a single agent, neither vinflunine total blood clearance nor trastuzumab serum concentrations were modified when the drugs were combined. All patients were evaluable, and the overall response rate was 73.3 % (95 % CI 54.1-87.7). The median progression-free survival was 11.3 months (95 % CI 9.4-21.0). At the dose of 280 mg/m(2), grade 3-4 neutropenia were seen in 4 patients (44.4 %) without febrile neutropenia. Non-hematologic grade 4 toxicities were not reported while grade 3 peripheral sensory neuropathy concerned 2 patients (22.2 %).. The RD of vinflunine in combination with the standard regimen of trastuzumab is 280 mg/m(2) every 3 weeks. No mutual PK drug-drug interaction was seen. This regimen appears to be active with a favorable safety profile. Its role in HER2-positive MBC treatment needs to be defined in prospective comparative clinical trials.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Drug Interactions; Female; Humans; Middle Aged; Neoplasm Metastasis; Receptor, ErbB-2; Trastuzumab; Vinblastine

Vinfunine (VFL) is a novel bifluorinated tubulin-targeted agent of the vinca alkaloids class active in advanced stage breast cancer. We conducted a phase I study combining VFL with doxorubicin (DXR) to define the recommended dose (RD), safety, pharmacokinetic (PK) interaction and efficacy. Two schedules (day 1 every 3 weeks; days 1 and 8 every 3 weeks) were investigated as first line chemotherapy in metastatic breast cancer patients. Thirty-two patients received a total of 162 cycles of the VFL-DXR combination (median 6). The RDs were VFL 250 mg/m(2)/DXR 40 mg/m(2) every 3 weeks for schedule 1 and VFL 120 mg/m(2)/DXR 25 mg/m(2) days 1 and 8 every 3 weeks for schedule 2. The main dose-limiting toxicity was neutropenia. The most frequent non-hematological adverse events were nausea, fatigue, constipation, vomiting, anorexia, stomatitis and dyspnea. Objective response rate was reached in 47.1% of the patients. No PK interaction was observed. VFL-DXR combination is feasible with manageable toxicity. The antitumor activity was promising and supports further evaluation.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Doxorubicin; Drug Administration Schedule; Female; Humans; Middle Aged; Vinblastine

We investigated the microtubulin inhibitor vinflunine—with trastuzumab in human epidermal growth factor receptor-2 (HER2)-positive patients—as first-line metastatic breast cancer therapy. HER2-negative patients received vinflunine on day 1; HER2-positive patients received vinflunine/trastuzumab every 21 days. Forty-eight patients in each treatment group were planned; the sponsor terminated the study early. Thirty-two evaluable patients (vinflunine, 11; vinflunine/trastuzumab, 21) were enrolled. In HER2-positive patients, vinflunine/trastuzumab produced an objective response rate (33%), clinical benefit rate (71%), and progression-free survival (6.2 months). Grade-3/4 neutropenia occurred in 14 (44%) patients; gastrointestinal toxicities were common and six patients were hospitalized for treatment-related toxicity. The vinflunine/trastuzumab combination was active and well tolerated, but our results do not suggest advantages over taxane/trastuzumab or vinorelbine/trastuzumab.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Middle Aged; Neoplasm Metastasis; Neutropenia; Pain; Receptor, ErbB-2; Trastuzumab; Treatment Outcome; Vinblastine

A multicenter, open-label, phase 2 study evaluated the efficacy and safety of intravenous vinflunine as third-line treatment in patients with progressing metastatic breast cancer (MBC) after failure of anthracycline- and taxane-based chemotherapy.. Fifty-six patients with MBC, relapsing after receiving 2 previous treatments for advanced disease, including both anthracyclines and taxanes, received 320 mg/m(2) of vinflunine once every 3 weeks (median number of 2.5 cycles, range: 1-13).. According to an independent radiologist, the response rate was 12.5% (95% CI: 5.2-24.1) and 14% (95% CI: 5.3-27.9) (6 partial responses) in the treated and evaluable populations, respectively. Disease control was achieved in 42.9% and 51.2% of the patients, respectively. Median progression-free survival was 2.6 months (95% CI: 1.6-4.0 months) with a median overall survival of 11.4 months (95% CI: 7.4-14.2 months). Duration of response was 6.8 months (95% CI: 5.6 months, upper limit not reached). Leukopenia was the most frequent hematologic toxicity, with grade 3/4 severity in 49.1% of the patients. Grade 3 neutropenia in 30.9%, grade 4 in 40.0% of patients, febrile neutropenia (5.4%), and 1 case of neutropenia infection (1.8%) were reported. Other grade 3 toxicities included anemia (5.5%), fatigue (14.3%), and constipation (7.1%), which were noncumulative. The adverse events associated with vinflunine were predictable and manageable.. Vinflunine is an active and well-tolerated agent as third-line treatment of patients with MBC after failure of anthracycline- and taxane-based therapy. These results warrant further investigation of vinflunine monotherapy or in combination for the treatment of MBC.

Topics: Adult; Aged; Anthracyclines; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Breast Neoplasms; Bridged-Ring Compounds; Female; Humans; Middle Aged; Neoplasm Staging; Taxoids; Treatment Failure; Vinblastine

To evaluate the single agent activity, pharmacokinetics and tolerability of the novel tubulin targeted agent vinflunine (VFL) (320 mg m(-2) q 21 days) as second-line chemotherapy in patients with metastatic breast carcinoma (MBC). All patients had disease progression after anthracycline/taxane (A/T) therapy. They could have received a nonanthracycline adjuvant treatment and subsequently received a first-line A/T combination for advanced/metastatic disease; or relapsed >6 months after completion of adjuvant A/T therapy and were subsequently treated with the alternative agent; or relapsed within 6 months from an adjuvant A/T combination. Objective response was documented in 18 of 60 patients enrolled (RR: 30% (95% confidence interval (CI): 18.9-43.2%)). Among the responders, seven patients had relapsed during a period of <3 months from taxane-based regimen yielding a RR of 33.3%. The median duration of response was 4.8 months (95% CI: 4.2-7.2), median progression-free survival was 3.7 months (95% CI: 2.8-4.2) and median overall survival was 14.3 months (95% CI: 9.2-19.6). The most frequent adverse event was neutropenia (grade 3 in 28.3% and grade 4 in 36.7% of patients). No febrile neutropenia was observed. Fatigue (grade 3 in 16.7% of patients) and constipation (grade 3 in 11.7% of patients) were also common; these were non-cumulative and manageable permitting achievement of a good relative dose intensity of 93.5%. Vinflunine is an active agent with acceptable tolerance in the management of MBC patients previously treated with (A/T)-based regimens. These encouraging phase II results warrant further investigation of this novel agent in combination with other active agents in this setting or in earlier stages of disease.

Topics: Adult; Aged; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Constipation; Disease Progression; Female; Humans; Leukopenia; Middle Aged; Nausea; Neutropenia; Survival Analysis; Taxoids; Treatment Outcome; Vinblastine

Vinca alkaloids are an important class of anticancer agents and semisynthetic vinca alkaloids are developed to improve the therapeutic index of this class of drugs. In the present study, a direct comparison was made between vinflunine and vinorelbine regarding their radiosensitizing and cell cycle effects.. Four human tumour cell lines were tested under identical experimental conditions, using equitoxic concentrations of vinflunine and vinorelbine.. Vinflunine and vinorelbine induced a comparable radiosensitizing effect (p-value never below 0.01) when cells were incubated for 24 h immediately prior to radiation. Regarding the cell cycle effects, a statistically significant concentration-dependent G2/M block was seen after 24 h incubation with vinorelbine in all tested cell lines. Similar results, with small cell line-related differences, were observed with vinflunine.. The radiosensitizing effects of both semisynthetic vinca alkaloids were comparable (not statistically different) and nearly always cell line-specific and concentration-dependent. The cell cycle effects could be related to the observed radiosensitizing effects. Considering the more favourable toxicity profile of vinflunine, this agent might be more promising than vinorelbine for chemoradiation studies in the clinic.

Topics: Antineoplastic Agents, Phytogenic; Breast Neoplasms; Carcinoma; Carcinoma, Non-Small-Cell Lung; Cell Cycle; Cell Line, Tumor; Dose-Response Relationship, Drug; Female; Gamma Rays; Humans; Lung Neoplasms; Microtubules; Molecular Structure; Radiation-Sensitizing Agents; Structure-Activity Relationship; Tongue Neoplasms; Urinary Bladder Neoplasms; Vinblastine; Vinorelbine