ErbB2+ metastatic breast cancer treatment after progression on trastuzumab: a cost-effectiveness analysis for a developing country / Tratamientos para cáncer de seno metastásico ErbB2+ en progresión Post-Trastuzumab: Análisis de costo-efectividad para un país en vía de desarrollo

Objective Breast cancer (BC) and metastatic breast cancer (MBC) are significant causes of deaths amongst women worldwide, including developing countries. The cost of treatment in the latter is even more of an issue than in higher income countries. ErbB2 overexpression is a marker of poor prognosis and the goal for targeted therapy. This study was aimed at evaluating the cost-effectiveness in Colombia of ErbB2+ MBC treatment after progression on trastuzumab. Methods A decision analytic model was constructed for evaluating such treatment in a hypothetical cohort of ErbB2+MBC patients who progressed after a first scheme involving trastuzumab. The alternatives compared were lapatinib+capecitabine (L+C), and trastuzumab+a chemotherapy agent (capecitabine, vinorelbine or a taxane). Markov models were used for calculating progression-free time and the associated costs. Effectiveness estimators for such therapy were identified from primary studies; all direct medical costs based on national fees-guidelines were included. Sensitivity was analyzed and acceptability curves estimated. A 3 % discount rate and third-payer perspective were used within a 5-year horizon. Results L+C dominated its comparators. Its cost-effectiveness ratio was COP $49,725,045 per progression-free year. The factors most influencing the results were the alternatives' hazard ratios and the cost of trastuzumab. Conclusion Lapatinib was cost-effective compared to its alternatives for treating MBC after progression on trastuzumab using a Colombian decision analytic model.

Objetivo El cáncer de seno (CS) y cáncer de seno metastásico (CSM) son importantes causas de muerte entre las mujeres a nivel mundial y en países en vía de desarrollo. En estos últimos los costos de los tratamientos son aún más preocupantes que en países de alto ingreso. La sobreexpresión de ErbB2 es marcador de pobre pronóstico y objetivo de terapias dirigidas. Se evaluó la costo-efectividad de los tratamientos de CSM ErbB2+ en progresión post-trastuzumab en Colombia. Métodos Se desarrolló un modelo analístico de decisiones para evaluar los tratamientos en una cohorte hipotética de CSM ErbB2+ que progresaron después de un primer esquema con trastuzumab. Las alternativas comparadas fueron: lapatinib+capecitabina (L+C), y trastuzumab más un agente quimioterápico (capecitabina, vinorelbinao un taxano). Se usaron modelos de Markov para calcular el tiempo libre de progresión y los costos asociados. Estimaciones de efectividad fueron identificadas de estudios primarios. Se incluyeron todos los costos médicos directos basados en los manuales tarifarios nacionales. Se realizaron análisis de sensibilidad y curvas de aceptabilidad. Se descontaron costos y resultados a una tasa anual de 3 %, la perspectiva de análisis fue del tercer pagador y el horizonte de 5 años. Resultados L+C domina a sus comparadores con un razón de costo-efectividad de COP $49 725 045 por año libre de progresión. Los factores que más influencian los resultados son los hazard ratios de las alternativas y el costo de trastuzumab. Conclusión Lapatinib es costo-efectivo comparado con sus alternativas para el tratamiento del CSM después de la progresión con trastuzumab en el escenario colombiano.

multicentre phase-II feasibility study evaluating gemcitabine/ vinorelbine / prednisolone combination chemotherapy in relapsed / refractory Hodgkin's lymphoma

To determine the efficacy and toxicity of Gemcitabine, Vinorelbine and Prednisolone [GVP] salvage chemotherapy in relapsed / refractory Hodgkin's Lymphoma [HL]. A phase-II non-randomized single arm study. This study was conducted at Combined Military Hospital and Medical College Lahore, Mayo Hospital, King Edward Medical University, Lahore, Allied Hospital, Punjab Medical College, Faisalabad and Combined Military Hospital, Rawalpindi, from January 2007 to December 2007. Fifty adult patients with relapsed/refractory HL, adequate marrow reserve, hepatorenal and pulmonary functions, with radiological measurable disease and Karnofsky performance status of 0 - 2 non-candidates for stem cell transplantation, were enrolled. Four 28 days cycles of GVP [Gemcitabine 1000 mg/m2, Vinorelbine 30 mg/m2 on day 1 and 8 intravenously with oral Prednisolone 100 mg/day on day 1 - 5] were given. Response evaluation done according to Cotswolds meeting recommendations and toxicity was evaluated with NCI-CTC [National Cancer Institute - Common Terminology Criteria for adverse events v 3.0]. Forty patients completing 4 cycles of GVP, 14 refractory/early relapse and 26 late relapsed [one year postprimary treatment with ABVD] were available for evaluation. The overall response [CRu+PR] rate was 77.5% with better response 85% in late relapsed patients. Haematological toxicity was most common and seen in 70% of cases. GVP is well-tolerated regimen with high response rate and needs to be tested in late relapsed H

Evaluation of the protective effect of isoprinosine against navelbine induced oxidative stress in mice

Many studies in vitro and in vivo have shown immunomodulating and antiviral activities of Isoprinosine [inosine pranobex]. Chemotherapy means the use of a drug which is most effective at, killing cells that are rapidly dividing. Vinorelbine [Navelbine, 5 oranhydrovinblastine] is a third-generation vinca alkaloid anti-tumor drug. It is widely used in the treatment of cancer such as advanced non-small-cell lung cancer [NSCLC] and advanced breast cancer. The aim of this study was to determine the possible protective effects of Isoprinosine in bacterially infected and non infected mice at a dose level of 8.75 mg/kg/day orally every second day for 15 days under the effect of anticancer Navelbine. Mitochondrial DNA fragmentation, Lipid pereoxidation [MDA], glutathione contents [GSH], phagocytosis test and serum level of immunoglobulin G and M antibodies were evaluated, a significant increase in liver homogenate and mitochondria protein carbonyl levels was observed in Navelbine alone treated mice when compared to control group. DNA fragmentation in homogenate and mitochondria was significantly increased in all test groups when compared to control group except Isoprinosine treated animal group which showed significant decrease in DNA fragmentation. The results of this study proved the immune protective and immunomodulatory effects of Isoprinosine against Navelbine induced toxicity in Pseudomonas aeruginosa infected and non infected mice

Combination of oral vinorelbine and capecitabine in the treatment of metastatic breast cancer patients previously exposed to anthracyclines: a pilot study

Vinorelbine and capecitabine are both active in breast cancer with moderate toxicity. A pilot study conducted from December 2007 to January 2010 in patients with metastatic breast cancer [MBC] to the evaluate efficacy and safety of combination therapy with vinorelbine and capecitabine. The study included patients with MBC who were previously treated by anthracyclines either during the adjuvant phase or the metastatic phase. Patients were treated with oral vinorelbine [[60 mg/m[2]] on day 1+8 and capecitabine [1000 mg/m[2]] twice daily [VC] from day 1 to day 14 with both repeated every 3 weeks until progression, refusal or for a maximum of 8 cycles. A dose reduction was made in case of grade 3 and 4 toxicities. Of 31 women [median age, 51 years], 12 cases were first-line therapy and 19 cases were second-line therapy or greater, and 30 were evaluable for response. Two patients [6.4%] achieved complete response and 15 patients [48.4%] had a partial response giving an overall response rate of 54.8% [95% Cl, 42%-68%]. Time-to-disease progression was 7.8 months for patients receiving VC as first-line therapy versus 6 months for patients receiving VC as second-line therapy or more, while median survival time was 22 months and 10 months for the two groups, respectively. The oral VC regimen is effective and safe in patients with MBC previously exposed to anthracyclines, and offers a promising alternative to the intravenous route. Its role as a salvage therapy following anthracy-cline failure or as first-line chemotherapy requires further study

phase II study of gemcitabine combined with vinorelbine as first-line chemotherapy for metastatic breast cancer

There is an unmet need for new combination treatments, especially for aggressive, visceral, and high tumor burden metastatic breast cancer. Gemcitabine [GEM] has shown synergy with vinorelbine [VRL] in preclinical models, and has a toxicity profile that is different from VRL, another recently approved cytotoxic drug that seems to be effective in the treatment of breast cancer. We studied the efficacy and side effects of the GEM-VRL combination as first-line chemotherapy in patients in an openlabel, single arm, phase II study in patients with locally advanced or metastatic breast cancer who had been previously treated with an anthracycline-based regimen in the adjuvant/neoadjuvant setting. Of the 74 patients enrolled, 72 patients were evaluable for the primary treatment outcome [tumor response rates]. Four patients [6%] had a complete response and 26 patients [36%] had a partial response. Nineteen patients [26%] had stable disease. The median time to disease progression was 37 weeks [range, 1 -60 weeks]. Median duration of response was 43 weeks [range, 8.6 to 55 weeks] and one-year survival was 77% [95% confidence interval, 64% to 86%]. Grade 3-4 neutropenia without fever was reported in 10% of patients, thrombocytopenia in 1%, and febrile neutropenia in 11%. The most common clinical grade 3-4 toxicities were nausea [24%] and diarrhea and stomatitis [11% each]. Hospitalizations for adverse events mainly due to anemia, febrile neutropenia, septic shock and hepatic failure occured in 7%. With an overall response rate of 42%, the GEM-VRL combination had promising efficacy and good tolerability in metastatic breast cancer patients

Improved compliance with adjuvant vinorelbine and cisplatin in non-small cell lung cancer

Poor compliance has been a common feature in clinical trials of adjuvant chemotherapy for NSCLC with only 48% to 69% of patients completing all planned cycles. We retrospectively evaluated compliance and toxicity of platinum-based chemotherapy in the 2 years following recent reports of successful adjuvant chemotherapy trials for NSCLC. Patients who received adjuvant chemotherapy after complete resection of NSCLC between May 2003 and May 2005 were analyzed retrospectively. Patient demographics, ECOG status, stage, pathologic subtype and type of surgery were recorded. The number of chemotherapy cycles, delays, dose reducttions and change of chemotherapy were reported. Fifty patients were identified. The median age was 62 years [38% stage I, 18% stage II, 30% stage III and 14% had multiple primary tumors of variable stages]. Twenty percent were ECOG PS2; Only 12% had undergone pnemonectomy. Forty-one patients [82%] started cisplatin/vinorelbine [three switched to carboplatin because of nephrotoxicity, and one switched to carboplatin/paclitaxel because of fatigue and vomiting]. Three patients received other cisplatin-based combinations; six received carboplatin-based treatment [one each beccause of advanced age and cardiac dysfunction and 4 because of preexisting neuropathy]. Eighty percent comppleted all treatment; 40% required a dose reduction and 58% required delays in treatment. Six events of febrile neutropenia were reported in 5 patients and 5 patients required admission for toxicity. There were no toxic deaths. Multivariate analysis showed no effect of age, gender, extent of surgery or ECOG status on compliance, need for treatment modification or toxicity. Compared to historical trials, adjuvant platinum-based chemotherapy for resected NSCLC is now accepted by patients and physicians with a high degree of compliance

[Treatment of hormone-resistant prostate cancer]

Two recent randomized Phase-three studies [TAX 327 and SWOG 9916] have demonstrated that Docetaxel improved the survival rate of patients with hormone-resistant prostate cancer. Other drugs such as Mitoxantrone, vinorelbine, saraplatin and Epothilone are recommended as second-line treatment where Docetaxel treatment has failed. Treatment with Atrasentan, an endothelin-receptor antagonist, or other inhibitors of angiogenesis combined with Docetaxel is presently under evaluation. Zoledronic acid, alone or in association with chemotherapy, and the use of radioisotopes [strontium-89, samarium 153 and radium 223] are palliative treatment options for multiple painful bone metastases in hormone-resistant cancer. Collectively, these treatment options reduce the risk of mortality, prevent the complications associated with disease progression and improve the patients' quality of life. Better understanding of the alternative pathways for androgen receptor signaling, the role of estrogen receptors, cytokines and stromal growth factors contributing to hormone resistance may lead to new treatment strategies

Capecitabine plus vinorelbine combination therapy in patients with metastatic breast cancer pretreated with anthracyclines and/or taxanes

To determine efficacy and safety of capecitabine plus vinorelbine in metastatic breast cancer [MBC] patients who relapse after adjuvant and/or first line chemotherapy [including anthracyclines and/or taxanes]. From April 2007 to March 2003, 26 eligible patients were recruited. Patients were treated by Vinorelbine in a dose of 25 mg/m[2] administered on days 1 and 8 every 3 weeks with Capecitabine orally twice daily [1000 mg/m[2]] for 14 consecutive days starting on day 1 of the cycle. The median age was 56 years [range 31-67]; ECOG PS 0-1, [9-12]; ER/PR +ve [19]; prior chemotherapy anthracvcyclines/taxanes [26/8]. After chemotherapy the overall response rates were 48% [1 CR and 11PR] [95% confidence interval [CI], 35.9-59.7]. In additional seven patients [28%] showed disease stabilization. The median time to disease progression was seven months and median overall survival was 17.5 months. Myelosuppression was the predominant toxicity. Toxicities included grades III and IV neutropenia in 7 [2 7%] and 3 [11.5%] patients respectively, and only one patient developed febrile neutropenia. Grade III hand-foot syndrome occurred only in One patient. Other nonhematologic toxicities were minimal and manageable. This study demonstrated that capecitabine plus vinorelbine combination was effective and well tolerated in MBC patients even after failure of anthracycline-and/or taxane-containing regimens

Capecitabine and Vinorelbine in Patients with Metastatic Breast Cancer Previously Treated with Anthracycline and Taxane

We have evaluated the efficacy and safety of the combination of capecitabine and vinorelbine in metastatic breast cancer (MBC) patients previously treated with anthracycline-and taxane-containing regimens. Between April 2000 and September 2002, 44 female MBC patients received oral capecitabine (1,250 mg/m(2) twice daily on days 114), and intravenous vinorelbine (25 mg/m2 on days 1 and 8) during each 3 weekchemotherapy cycle (median, 5 cycles/patient; total, 235 cycles). One patient achieved a complete response and 21 patients had partial responses, giving an overall response rate of 50% in the intention-to-treat analysis (95% CI, 35.0-65.0%). Median duration of response was 6.0 months (range 1.2-23.0 months). Patients were followed- up for a median of 16 months, with median progression-free survival being 5.3 months, and median overall survival being 17 months. Toxicities included grades III and IV neutropenia in 63 (26.8%) and 4 (1.7%) cycles, respectively, and grades II and III hand-foot syndrome in 12 (5.1%) and 4 (1.7%) cycles, respectively. Other nonhematologic toxicities were minimal and manageable. In conclusion, the combination of capecitabine and vinorelbine was effective and well tolerated in MBC patients even after treatment with anthracyclines and taxanes.

Quality of life and efficacy of vinorelbine and fluorouracil versus fluorouracil, adriamycin and cyclophosphamide chemotherapy in advanced breast cancer

To assess the effect of vinorelbine and 5-fluorouracil [NF] in comparison to 5-fluorouracil, adriamycin and cyclophosphamide [FAC] chemotherapy regimen on the treatment outcome and their impact on the quality of life in patients with advanced breast cancer [ABC]. The prognostic significance of the quality of life on survival was also studied. It is a phase Ill study that included 104 women with ABC who were randomly assigned to receive either FAC [Group I] or NF regimen [Group II]. Patients were evaluated for response rate [RR], time to tumor progression [TTP], overall survival [OS] and toxicities. The quality of life was assessed using Spitzer's quality of life index [QLI]. Patients who received FAC achieved significantly higher overall RR, compared to those who received NF regimen [69.2% versus 50.0%, p=0.04]. A significantly higher median TTP was achieved in patients who received FAC compared to those received NF [11.4 and 6.1 months] respectively with p=0.03. A higher median OS was observed in group I patients compared to group II 19.0 versus 16.4 months, however, the difference in OS was not statistically significant [p=0.4]. The quality of life index [QLI] was proved to be an independent factor affecting TTP in group I [p=0.001] and in group II as well [p=0.01] As regards OS, QLI has no significant prognostic influence in either groups. Since improvement in TTP is a major goal where treatment is mainly palliative, our impression is that FAC is still one of the standard anthracycline-containing regimens in ABC. Vinorelbine, 5-fluorouracil can be used as second-line or as first-line regimen in cases where anthracyclines are not appropriate. Quality of life can be used as a predictor for progression-free survival

Evaluation of vinorelbine and doxorubicin as first line treatment for metastatic breast cancer in Suez Canal Area

Forty three patients with metastatic breast cancer, 25 premenopausal, 18 post menopausal who had received no prior chemotherapy except CMF [cyclophosphamide, methotrexate and 5-fluoromacil] as adjuvant treatment for their disease were included in this study. Navelbine was administered at 25 mg/m[2] by thirty minutes intravenous infusion on days I and 8 and doxorubicin at 50 mg/m[2] by slow IV infusion on day I with each course repeated at 3 weeks intervals. Patients were treated for a maximum 11 cycles. Objective overall response was seen in 30 patients. Complete response [CR] was seen in 9 patients [20%] and partial response [PR] in 21 patients [48%]. Overall response was seen in both visceral and non visceral metastases, 18 out of 20 patients [90%] and 12 out of 23 patients [52%] respectively. The response rate is not affected by the extent of the disease. The main dose limiting toxicity was neutropenia, it was seen with its grade 3, 4 in 35% of the patients. We have no cardiac toxicity in our patients. while the other non hematological toxicity [alopecia, vomiting, constipation, neuropathy] were mild, and tolerable. Navelbine/doxorubicin is an active combination which is generally tolerated and can he strongly recommended for the management of those patients requiring an aggressive approach to control widespread metastatic breast cancer

Recent advances in cancer therapy

The treatment of cancer has developed substantially from its conception in the first years of the 20th century. Since the introduction of alkylating agents during second World War, the oncology specialty has markedly grown. In the recent years, new drugs have been approved for the treatment of cancer. Such examples include the taxanes (Docetaxel and Paclitaxel), Vinorelbine, Irinotecan, Topotecan, Gemcitabine and Gliadel. We will discuss these new chemotherapuetic agents, their pharmacology, indications, toxicity and appropriate dosing. There is no doubt that further clinical research is needed to determine the optimal use of these agents