vinflunine and Neoplasms

To review the pharmacology, pharmacokinetics, in vitro and in vivo efficacy, and safety profile of vinflunine in the treatment of various solid tumors.. A literature search was conducted using keywords included vinflunine, vinca alkaloid, Javlor, and solid tumor in PubMed/MEDLINE (1950-January 2009) and International Pharmaceutical Abstracts (1950-January 2009).. Published studies, posters, and meeting abstracts evaluating the in vitro and in vivo efficacy of vinflunine were reviewed.. Vinflunine is the newest member of the vinca alkaloid family. It has the weakest affinity to tubulins, but is shown to have unique receptor-independent antiangiogenesis, and antimetastasis properties. After administration, it is distributed extensively into tissues, metabolized via the CYP3A4 system, and eventually excreted in urine and feces. Phase II/III trials reported activities of vinflunine in advanced stage nonsmall-cell lung cancer, metastatic breast cancer, metastatic renal cell carcinoma, transitional cell carcinomas of the urothelium, small-cell lung cancer, and malignant pleural mesothelioma as monotherapy and in combination with other chemotherapy agents. More ongoing trials are evaluating its use in other solid tumors and in combination regimens. The most common adverse events in these trials were hematological (anemia and neutropenia), constipation, fatigue, abdominal pain, and myalgia.. Vinflunine is a new vinca alkaloid for the treatment of advanced staged solid tumors. Available data showed promising activities in various malignancies. Further studies are needed to further define vinflunine's role in oncology.

Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Humans; Neoplasms; Treatment Outcome; Tubulin Modulators; Vinblastine

Vinca alkaloid agents have been widely used in several different types of malignancies. However, cancer cells, ultimately, develop resistance to these agents. Therefore, the development of new agents with improved efficacy is warranted. Recently, a new synthetic vinca alkaloid, vinflunine, was developed through the addition of two fluor molecules by superacidic chemistry.. The authors describe the development of the new vinca alkaloid vinflunine from preclinical studies to the late-stage clinical trials, highlighting the most important clinical and safety data of vinflunine. In vitro and in vivo studies have shown a superior efficacy of vinflunine over other vinca alkaloids and with an improved safety profile. Early clinical trials have demonstrated a significant activity of vinflunine against different malignancies. Phase III trials showed that vinflunine increases survival in patients with advanced transitional cell carcinoma of the urothelium (TCCU) tract treated in the second-line and is as effective as docetaxel in second-line NSCLC.. Vinflunine is currently approved in Europe for the treatment of second-line TCCU and is currently being developed in other malignancies. It has been shown to have predictable and manageable adverse effects, such as neutropenia, anemia, constipation and fatigue.

Topics: Animals; Clinical Trials as Topic; Drug Evaluation, Preclinical; Drug-Related Side Effects and Adverse Reactions; Humans; Neoplasms; Vinblastine; Vinca Alkaloids

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

Vinflunine is a novel second generation of Vinca alkaloid. The binding of vinflunine to tubulin and subsequent cellular arrest in mitosis is the core mechanism of this antineoplastic agent. In addition, its potential vascular-disrupting and antiangiogenic activities uphold further clinical development of this compound.. To review and summarise the pharmacological and latest clinical data, and discuss the impact of vinflunine on current treatment regimens.. A review of published literature and conference abstracts for results of previous preclinical and latest clinical studies in all cancer types was performed.. Noteworthy results from Phase II studies for treatment of non-small cell lung cancer (NSCLC), breast cancer and bladder cancer supported Phase III studies. One of the Phase III studies for treatment of advanced NSCLC showed important results. Encouraging results of combination use of vinflunine and other biologic agents also opened areas to investigate its synergistic or auxiliary role to existing therapies.

Topics: Animals; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Humans; Mitosis; Molecular Structure; Neoplasms; Treatment Outcome; Tubulin Modulators; Vinblastine

The acridone alkaloid acronycine, isolated from several Sarcomelicopespecies (Rutaceae) was shown to exhibit a promising activity against a broad spectrum of solid tumors. Nevertheless, subsequent clinical trials gave limited results, probably due to the moderate potency and poor water solubility of this drug. The isolation of the unstable acronycine epoxide from several New-Caledonian Sarcomelicope led to a hypothesis of bioactivation of acronycine by transformation of the 1,2-double bond into the corresponding oxirane in vivo. Consequently, we synthesized a series of cis-1,2-dihydroxy-1,2-dihydroacronycine diesters which exhibited interesting antitumor properties with a broadened spectrum of activity and an increased potency when compared with acronycine. The demonstration that acronycine should interact with DNA prompted us to develop benzo[b]acronycine analogs possessing an additional aromatic ring linearly fused on the natural alkaloid basic skeleton. In vivo, 1,2-dihydroxy-1,2-dihydrobenzo[b]acronycine esters and diesters, exemplified by cis-1,2-diacetoxy-1,2-dihydrobenzo[b]acronycine developed under the code S 23906-1, demonstated a marked antitumor activity in human orthotopic models of lung, ovarian and colon cancers xenografted in nude mice. The cytotoxic and antitumor activities of these compounds were strongly correlated with their ability to give covalent adducts with purified as well as genomic DNA. Such adducts involve reaction between the exocyclic N-2 amino group of guanines exposed in the minor groove of double helical DNA and the leaving ester group at the benzylic position 1 of the drug.

Topics: Animals; Antineoplastic Agents, Phytogenic; Humans; Neoplasms; Vinblastine

Vinflunine is the first bi-fluorinated, tubulin-targeted agent that was obtained by semisynthesis using super-acidic chemistry, which allowed the selective introduction of two fluorine atoms at the C20' position of vinorelbine. This compound has been selected for clinical development on the basis of promising preclinical activity that warranted a study in patients with a wide spectrum of solid tumours. Clinically significant activity was seen in the Phase II studies for the treatment of bladder, non-small cell lung and breast cancers, thus prompting the initiation of the Phase III trials that are currently ongoing.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Humans; Neoplasms; Tubulin Modulators; Vinblastine

Pierre Fabre SA, in collaboration with Bristol-Myers Squibb Co, is developing vinflunine, a fluorinated vinca alkaloid, as a potential anticancer agent.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Clinical Trials as Topic; Drug Delivery Systems; Endothelial Cells; Humans; Infusions, Intravenous; Neoplasms; Neovascularization, Physiologic; Vinblastine

Vinflunine (VFL) ditartrate, a novel tubulin-targeted inhibitor, is registered for the treatment of patients with advanced or metastatic urothelial transitional cell carcinoma. This phase I study assessed the effect of renal impairment on the pharmacokinetics and tolerability of VFL.. VFL was infused in patients with advanced/metastatic solid tumours once every 3 weeks with anticipated dose reduction on the first cycle stratified according to the creatinine clearance (CLcr ) values. Pharmacokinetic data were collected on the first two cycles in renally impaired patients (CLcr ≤ 60 ml min(-1) ) and were compared with a control cohort of patients (CLcr > 60 ml min(-1) ).. Thirty-three patients (46-86 years) were treated, 13 in group 1 (40 ml min(-1) ≤ CLcr ≤ 60 ml min(-1) ) and 20 in group 2 (20 ml min(-1) ≤ CLcr < 40 ml min(-1) ). The renal dysfunction induced a mean decrease in VFL clearance of 12% in group 1 and 28% in group 2, compared with the control group. The anticipated dose reduction given in renally impaired patients (i.e. 280 mg m(-2) and 250 mg m(-2) in groups 1 and 2, respectively) yielded similar drug exposure to control patients. The tolerance profile of VFL in patients with renal dysfunction was similar to that observed in patients with CLcr > 60 ml min(-1) .. In conclusion, the recommended doses of intravenous VFL administered once every 3 weeks in cancer patients with renal impairment are 280 mg m(-2) when CLcr is between 40 and 60 ml min(-1) and 250 mg m(-2) when CLcr is between 20 and <40 ml min(-1) .

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Phytogenic; Drug Administration Schedule; Female; France; Humans; Infusions, Intravenous; Kidney; Kidney Diseases; Male; Metabolic Clearance Rate; Middle Aged; Neoplasms; Treatment Outcome; Tubulin Modulators; Vinblastine

Vinflunine is a novel tubulin-targeted agent that is currently indicated as a monotherapy in bladder cancer patients. The recommended dose of 320 mg/m(2) is given as an intravenous infusion once every 3 weeks. Vinflunine is metabolized through CYP3A4 and mainly eliminated via the feces. A phase I trial was designed to explore the tolerability and pharmacokinetics of vinflunine in cancer patients with ranging degrees of liver dysfunction (LD). A sequential design was used for patient accrual, with the objective of determining the maximum tolerated dose (MTD) and the recommended dose (RD) of vinflunine in 3 groups of increasing LD levels. Vinflunine and its only active metabolite 4-O-deacetylvinflunine were quantified in serial whole blood samples. PK parameters were derived and compared between LD groups and with a reference PK database. Vinflunine and 4-O-deacetylvinflunine PK parameters were not affected in any of the explored LD levels. Geometric mean values for vinflunine total clearance were 47.8, 37.5 and 45.4 L/h in the 3 groups of increasing degrees of LD, as compared to 42.5 L/h in reference patients with no LD. No relationship was found between vinflunine clearance and the presence or absence of cirrhosis, nor was it found with the presence or absence of liver metastasis or with liver-related biochemical parameters. Based on the observed tolerability profile, the recommended doses of i.v. vinflunine are 320 mg/m(2), 250 mg/m(2) or 200 mg/m(2) for patients with increasing degrees of liver dysfunction.

Topics: Adult; Aged; Antineoplastic Agents, Phytogenic; Bilirubin; Female; gamma-Glutamyltransferase; Humans; Infusions, Intravenous; Liver Diseases; Male; Middle Aged; Neoplasms; Treatment Outcome; Tubulin Modulators; Vinblastine

Vinflunine ditartrate is a microtubule inhibitor belonging to the vinca alkaloid family. This phase I study was carried out to evaluate the maximal tolerated dose, the safety profile, the pharmacokinetics and the activity of oral vinflunine (VFL) given daily in patients with advanced/metastatic solid tumours and who have failed standard therapy.. Patients were treated with oral VFL administered once daily for 6 weeks followed by a two-week rest. Sequential dose-escalating cohorts of patients were enrolled into 5 dose levels: 20, 40, 60, 75 and 95 mg/day.. In total, 27 patients received 53 cycles. Dose-limiting toxicities (DLT) were observed from 60 mg/day. The dose levels 75 and 95 mg/day were both assessed as maximal tolerated dose. The most frequent dose-limiting toxicities were of haematological origin. The recommended dose was defined as 60 mg/day, dose at which 4 patients experienced long stabilizations (≥4 months) and also received longer treatment duration in comparison with the other dose levels. Blood exposure of VFL and its active metabolite 4-O-deacetyl vinflunine (DVFL) increased proportionally to the dose levels. The concentrations of VFL and DVFL reached a steady state at, respectively, 5 and 20 days and remained stable for the rest of the cycle. Increased incidence of DLT/SAE was consistent with the increase of VFL dose and drug exposure.. These results showed the feasibility of daily oral vinflunine administration on a 6-week treatment duration. This new schedule of administrations enabled sustained and stable blood concentrations of both VFL and DVFL. The recommended dose was defined at 60 mg/day, dose at which 4 patients experienced clinical benefit.

Topics: Adult; Aged; Anemia; Angiogenesis Inhibitors; Antineoplastic Agents, Phytogenic; Area Under Curve; Asthenia; Biotransformation; Dose-Response Relationship, Drug; Female; Half-Life; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Metastasis; Neoplasms; Neutropenia; Prospective Studies; Treatment Outcome; Vinblastine

Vinflunine is a new microtubule inhibitor of the vinca-alkaloid family. It is marketed in transitional cell carcinoma of urothelial tract as a 20 min infusion given every 3 weeks in Europe.. In this phase I study, vinflunine was administered to patients with advanced malignancies as hard capsules given twice a day on days 1-2 every week, with 3 weeks cycles. Serial blood samples were collected during the first cycle for pharmacokinetic investigations.. Thirty-six patients (pts) were treated at 6 dose levels 150 (3 pts), 190 (3 pts), 230 (8 pts), 300 mg/day (6 pts) and then 250 (3 pts) and 270 mg/day (13 pts). The Maximal Tolerated Dose (MTD) was reached at 300 mg/day where 2 patients out of 6 experienced a dose limiting toxicity (febrile neutropenia with diarrhea). The lower dose level of 270 mg/day was the recommended dose (RD), the toxicity profile being mainly anaemia, neutropenia, fatigue and constipation. The pharmacokinetic analysis demonstrated the adequacy of the flat-fixed dosing regimen, as no correlation between clearance of vinflunine and body surface area was evidenced. Blood concentrations and exposure increased with dose, and a pharmacokinetic accumulation was observed, which is consistent with the terminal half-life of the compounds. The inter-individual exposure variability at the RD was 35%.. Repeated weekly administration of oral vinflunine is feasible and exhibits a moderate inter-individual PK variability. The MTD was achieved at 300 mg/day given for 2 consecutive days. According to the protocol rules, the RD was established at 270 mg/day.

Topics: Adult; Aged; Capsules; Drug Administration Schedule; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Metastasis; Neoplasms; Tubulin Modulators; Vinblastine

Vinflunine is a new-generation microtubule inhibitor, which is currently registered in Europe and in some countries elsewhere as an intravenous formulation for the second-line treatment of transitional urothelial cell carcinoma. On the basis of favourable non-clinical results, the clinical development of an oral formulation was initiated.. The absolute oral bioavailability was investigated in patients through two consecutive trials: the first trial used soft gelatin capsules filled with solubilized vinflunine (SLCaps), while the second study investigated hard gelatin capsules containing vinflunine as a formulated powder (HPCaps).. Each pharmacokinetic trial was conducted according to a randomized cross-over design. Patients received 120 mg/m2 of either oral (SLCaps or HPCaps) or intravenous vinflunine on day 1, followed by the alternate dosing route after a 2-week washout period. Blood samples were collected over 168 hours. A pharmacokinetic analysis was conducted for each patient and route of dosing to derive the absolute oral bioavailability of SLCaps and HPCaps.. A total of 12 and 22 patients were enrolled, for SLCaps and HPCaps, respectively. Vinflunine absorption was rapid for both oral formulations. Blood concentrations peaked at 2.5 hours following oral intake with food, and then decreased similarly to the intravenous profile. The mean absolute bioavailability was high, at 58.3 ± 14.4% (SLCaps) and 57.3 ± 11% (HPCaps), with limited inter-individual variability (coefficient of variation = 25% and 19% for SLCaps and HPCaps, respectively). Neither sequence nor period effects were detected. The gastro-intestinal tolerance was satisfactory. The main drug-related adverse events were asthenia, fatigue, constipation and neutropenia, mostly of grade 1 or 2. No grade 4 and no drug-related serious adverse events were reported.. The high bioavailability and low inter-individual variability are favourable pharmacokinetic properties, which could be valuable for further clinical development of oral vinflunine.

Topics: Administration, Oral; Adolescent; Adult; Aged; Antineoplastic Agents, Phytogenic; Biological Availability; Capsules; Cross-Over Studies; Female; Gelatin; Humans; Injections, Intravenous; Male; Middle Aged; Neoplasms; Vinblastine

Vinflunine is a novel vinca alkaloid with promising single agent clinical activity. Pemetrexed has at least additive activity with other vincas. A phase I trial was undertaken to assess the safety of vinflunine and pemetrexed in patients with refractory solid tumors.. A standard 3-patient cohort dose escalation scheme was used to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of the vinflunine/pemetrexed combination. Pemetrexed 500 mg/m(2) was given with vinflunine 280 mg/m(2) (cohort 1), 300 mg/m(2) (cohort 2) or 320 mg/m(2) (cohort 3) on day 1 of a 21-day cycle.. 19 patients were enrolled, median age 58 years (range 32 to 77) and had a median of 3 (range 1-6) prior therapies. DLT occurred 1 of 6 pts in cohort 1 (thrombocytopenia, hyponatremia), 2 of 10 pts in cohort 2 (febrile neutropenia, hyponatremia, hyperbilirubinema; febrile neutropenia), and 2 of 3 pts in cohort 3 (febrile neutropenia, hypokalemia; febrile neutropenia). 1 pt in cohort 2 died prior to completion of cycle 1 likely from disease progression. Most common grade 3/4 adverse events were neutropenia (7), leukopenia (5). Febrile neutropenia occurred in 4 patients (21%). No objective responses were seen. Two patients (breast and lung) had prolonged stable disease for 25 and 20 cycles respectively.. Based on this experience we recommend vinflunine 300 mg/m(2) and pemetrexed 500 mg/m(2) in combination every 3 weeks for future study. At these doses, the combination of vinflunine and pemetrexed was tolerable in this heavily pretreated population. Hematologic toxicity, including febrile neutropenia, was prominent.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cytochrome P-450 CYP3A; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Female; Glutamates; Guanine; Humans; Male; Midazolam; Middle Aged; Neoplasms; Pemetrexed; Phenotype; Statistics, Nonparametric; Treatment Outcome; Vinblastine

Epidermal growth factor receptor (EGFR) inhibition may overcome chemotherapy resistance by inhibiting important anti-apoptotic signals that are constitutively activated by an overstimulated EGFR pathway.. This phase I dose escalation trial assessed the safety and efficacy of vinflunine, a novel vinca alkaloid microtubule inhibitor, with erlotinib, an EGFR tyrosine kinase inhibitor, in patients with refractory solid tumors.. Seventeen patients were treated, 10 with continuous erlotinib, and 7 with intermittent erlotinib. At dose level 1, vinflunine 280 mg/m(2) IV day 1 and erlotinib 75 mg PO days 2-21 ("continuous erlotinib") in 21 day cycles, two of four patients experienced DLTs. At dose level -1 (vinflunine 250 mg/m(2) every 21 days and erlotinib 75 mg/day), two of six patients experienced DLTs. The study was amended to enroll to "intermittent erlotinib" dosing: vinflunine day 1 and erlotinib days 2-15 of a 21 day cycle. Two of seven experienced DLTs and the study was terminated. One patient with breast cancer had a partial response; three had stable disease ≥ 6 cycles. All were treated in the continuous erlotinib group.. Given the marked toxicity in our patient population, the combination of vinflunine and erlotinib cannot be recommended for further study with these dosing schemas.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cytochrome P-450 CYP3A; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Erlotinib Hydrochloride; Female; Humans; Male; Middle Aged; Neoplasms; Phenotype; Quinazolines; Treatment Outcome; Vinblastine

Vinflunine is a novel vinca alkaloid developed through the selective modification of vinorelbine using super-acidic chemistry. In preclinical testing, vinflunine demonstrated significantly enhanced anti-tumour activity in human tumour xenograft models when compared to its parent compound. A phase I study was conducted to evaluate the safety and toxicity of vinflunine administered as a 10 minute intravenous infusion on days 1 and 8 every three weeks. Sixteen patients with advanced solid tumours were treated. Two of four patients experienced dose limiting toxicities (DLT) at 190 mg/m2 and this was established as the maximum tolerated dose (MTD). At the MTD, the DLT of vinflunine consisted of constipation and neutropenia. Fatigue was notable but not dose limiting. No objective responses were observed. A dose of 170 mg/m2 given on a day 1 and 8 schedule every three weeks would be suitable for future studies.

Topics: Adult; Aged; Antineoplastic Agents; Constipation; Female; Humans; Infusions, Intravenous; Male; Maximum Tolerated Dose; Middle Aged; Neoplasms; Neutropenia; Vinblastine

Vinflunine is a novel vinca alkaloid obtained by semi-synthesis using super-acidic chemistry to selectively introduce two fluorine atoms at the 20' position of vinorelbine. In human tumour xenografts, vinflunine showed definite antitumour activity in seven out of 11 tumours tested compared with three out of 11 for vinorelbine.. In this phase I study, vinflunine was administered to 31 patients with advanced malignancies as a 10-min i.v. infusion every 3 weeks according to an escalating schedule of doses between 30 and 400 mg/m(2).. Pharmacokinetic parameters and toxicities were assessed and, at 400 mg/m(2), three out of five patients experienced dose-limiting toxicity. At the maximum tolerated dose (MTD), i.e. 400 mg/m(2), the toxicity profile of vinflunine consisted mainly of mucositis, constipation and neutropenia of short duration. Vinflunine area under the curve increased as a proportion of the administered dose whereas no saturation of elimination was observed.. The MTD of vinflunine was achieved at 400 mg/m(2) every 3 weeks. According to protocol rules, the recommended dose was established at 350 mg/m(2). A preliminary assessment of first patients included in early phase II trials led to reduction of the recommended dose to 320 mg/m(2) every 3 weeks for further development of vinflunine. Three partial responses (two in breast carcinoma, one in renal cell carcinoma) suggest that activity is likely to be seen in less heavily pretreated patient populations.

Topics: Adult; Aged; Antineoplastic Agents; Constipation; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Male; Maximum Tolerated Dose; Middle Aged; Mouth Mucosa; Neoplasms; Neutropenia; Stomatitis; Vinblastine

In the past few years, innumerable novel anti-cancer agents have been developed. Some of them have successfully entered into clinical practice while some of them have failed for different reasons. Although, nowadays, cancer treatment still relies heavily on conventional chemotherapy and surgery, with increasing evidence of novel biologic agents which demonstrate its higher anti-cancer activity and fewer side effects, more and more efforts have been spent on development of different types of novel agents. Vinflunine, a novel fluorinated vinca alkaloid, carries mitotic-arresting and tubulin-interacting properties and was just approved for treating transitional cell carcinoma of the urothelial tract (TCCU) in Europe. It, however, took quite a long time to get an approval. Needless to say, TCCU, similar to other types of cancer, is a very complex and heterogeneous disease and therefore, a single drug can hardly eradicate a cancer. Translational research, a new scientific research method, creates a link between clinical and laboratory studies. The link helps us to investigate the change in tumor environment in response to treatment, select patients who are more responsive to a particular treatment and predict prognosis of a group of patients with similar tumor characteristics. It can not only improve the success of a treatment, but also maximize the potential of novel anti-cancer agents.

Topics: Antineoplastic Agents; Carcinoma, Transitional Cell; Drug Design; Humans; Neoplasms; Patient Selection; Translational Research, Biomedical; Urologic Neoplasms; Urothelium; Vinblastine

Topics: Antineoplastic Agents; Biomedical Research; Clinical Trials as Topic; Humans; Lung Neoplasms; Molecular Structure; Neoplasms; Vinblastine

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Benzamides; Bevacizumab; Clinical Trials as Topic; Erlotinib Hydrochloride; Female; Humans; Kinesins; Male; Neoplasms; Quinazolines; Vinblastine

The antitumour activity of vinflunine, 20',20'-dichloro-3',4'-dihydrovinorelbine, a fluorinated Vinca alkaloid obtained by reaction in superacid media, was evaluated in comparison with vinorelbine against a series of subcutaneously-implanted human tumour xenografts. The tumours studied were established from bladder (BXF1299), pancreas (PAXF546), kidney (RXF944LX), colon (DLD-1, HT-29, TC37), central nervous system (SF-295), small cell lung (NCI-H69) and prostate (PC-3). Vinflunine or vinorelbine was administered as four weekly intraperitoneal treatments, within dose ranges of 5-80 or 0.63-10 mg/kg/injection, respectively. The overall antitumour activity of vinflunine was superior to that of vinorelbine. Vinflunine showed high activity against RXF944LX and NCI-H69 xenografts and moderate activity against PAXF546, PC-3 and TC37 tumours, achieving an overall response of 64%. This contrasts with a 27% response with vinorelbine, which proved only moderately active against RXF944LX and TC37 xenografts. These results confirm and extend our previous report of the broad spectrum of in vivo antitumour activity of vinflunine and reinforce its potential as a valuable addition to current chemotherapeutic agents.

Topics: Animals; Antineoplastic Agents, Phytogenic; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Female; Humans; Mice; Mice, Nude; Neoplasm Transplantation; Neoplasms; Transplantation, Heterologous; Vinblastine; Vinorelbine