taxane and vinflunine

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

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

Perioperative chemotherapy is likely to improve survival in both the neoadjuvant and the adjuvant setting. Therefore, it is an integral part of the modern treatment of patients with muscle-invasive urothelial bladder cancer. All patients who are suitable for cisplatin-based chemotherapy should be involved in a corresponding concept.Cisplatin-based combinations are standard regimens in the perioperative and palliative systemic treatment of urothelial cancer. Carboplatin is only an inferior substitute for "unfit" patients in the palliative treatment situation. Vinflunine may be used as a second-line agent in case of recurrence after palliative first-line treatment or in patients presenting with rapid progression after perioperative treatment. Alternatively, taxane or taxane-based combinations can be used in these situations.New therapeutic options may include the use of immune checkpoint inhibitors, which have shown promising results in early studies. Two substances have already been approved by the FDA for the treatment of advanced/metastatic urothelial cancer following platin-based upfront treatment. Other future options may be "tailored" treatment concepts based on the molecular pathogenesis of the individual patient. However, extensive pre-clinical work is still required for this approach.. Eine perioperative Chemotherapie verbessert wahrscheinlich sowohl in einem neoadjuvanten als auch in einem adjuvanten Konzept das Überleben des Patienten. Damit ist sie ein integraler Teil der modernen Therapie von Patienten mit einem muskelinvasiven Harnblasenkarzinom. Jeder Patient, der für eine Cisplatin-basierte Chemotherapie geeignet ist, sollte in ein entsprechendes Konzept eingebunden werden.Standard sowohl in der perioperativen als auch in der palliativen Systemtherapie des Urothelkarzinoms sind Cisplatin-basierte Kombinationstherapien. Carboplatin stellt nur bei „unfitten“ Patienten in der palliativen Therapiesituation einen möglichen Ersatz dar, in der perioperativen Systemtherapie besitz es keinen Stellenwert. Im Falle eines Rezidivs nach einer palliativen Erstlinientherapie oder bei einem schnellen Progress nach perioperativer Therapie kann eine Zweitlinientherapie mit Vinflunin durchgeführt werden. Alternativ dazu können auch Taxane oder Taxan-basierte Kombinationen zum Einsatz kommen.Neue Therapiemöglichkeiten sind der Einsatz von Immuncheckpoint-Inhibitoren, welche in ersten Studien vielversprechende Ergebnisse zeigten. Erste Zulassungen durch die FDA sind für die Therapie des metastasierten/fortgeschrittenen Urothelkarzinoms bereits erfolgt. Andere zukünftige Optionen sind „maßgeschneiderte“ Therapiekonzepte, die auf der Molekularpathogenese des individuellen Patienten beruhen. Hier sind jedoch noch weitreichende präklinische Arbeiten erforderlich.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Cisplatin; Humans; Neoadjuvant Therapy; Taxoids; Urinary Bladder Neoplasms; Vinblastine