Selecting first-line bevacizumab-containing therapy for advanced breast cancer: TURANDOT risk factor analyses.

BACKGROUND: The randomised phase III TURANDOT trial compared first-line bevacizumab-paclitaxel (BEV-PAC) vs bevacizumab-capecitabine (BEV-CAP) in HER2-negative locally recurrent/metastatic breast cancer (LR/mBC). The interim analysis revealed no difference in overall survival (OS; primary end point) between treatment arms; however, progression-free survival (PFS) and objective response rate were significantly superior with BEV-PAC. We sought to identify patient populations that may be most appropriately treated with one or other regimen. METHODS: Patients with HER2-negative LR/mBC who had received no prior chemotherapy for advanced disease were randomised to either BEV-PAC (bevacizumab 10 mg kg(-1) days 1 and 15 plus paclitaxel 90 mg m(-2) days 1, 8 and 15 q4w) or BEV-CAP (bevacizumab 15 mg kg(-1) day 1 plus capecitabine 1000 mg m(-2) bid days 1-14 q3w). The study population was categorised into three cohorts: triple-negative breast cancer (TNBC), high-risk hormone receptor-positive (HR+) and low-risk HR+. High- and low-risk HR+ were defined, respectively, as having ⩾2 vs ⩽1 of the following four risk factors: disease-free interval ⩽24 months; visceral metastases; prior (neo)adjuvant anthracycline and/or taxane; and metastases in ⩾3 organs. RESULTS: The treatment effect on OS differed between cohorts. Non-significant OS trends favoured BEV-PAC in the TNBC cohort and BEV-CAP in the low-risk HR+ cohort. In all three cohorts, there was a non-significant PFS trend favouring BEV-PAC. Grade ⩾3 adverse events were consistently less common with BEV-CAP. CONCLUSIONS: A simple risk factor index may help in selecting bevacizumab-containing regimens, balancing outcome, safety profile and patient preference. Final OS results are expected in 2015 (ClinicalTrials.gov NCT00600340).

Safety results from a phase III study (TURANDOT trial by CECOG) of first-line bevacizumab in combination with capecitabine or paclitaxel for HER-2-negative locally recurrent or metastatic breast cancer.

BACKGROUND: We report safety data from a randomised, phase III study (CECOG/BC.1.3.005) evaluating first-line bevacizumab plus paclitaxel or capecitabine for locally recurrent or metastatic breast cancer. PATIENTS AND METHODS: Patients aged ≥18 years with human epidermal growth factor receptor-2-negative breast adenocarcinoma were randomised to Arm A: bevacizumab 10 mg/kg days 1 and 15; paclitaxel 90 mg/m(2) days 1, 8, and 15, every 4 weeks; or Arm B: bevacizumab 15 mg/kg day 1; capecitabine 1000 mg/m(2) b.i.d., days 1-14, every 3 weeks, until disease progression, unacceptable toxicity or consent withdrawal. RESULTS: A post hoc interim safety analysis included 561 patients (Arm A: 284, Arm B: 277). The regimens demonstrated similar frequencies of all-grade and serious adverse events (SAEs), but different safety profiles. Treatment-related events occurred in 85.2% (Arm A) and 78.0% (Arm B) of patients. Fatigue was most common in Arm A (30.6% versus 23.5% Arm B), and hand-foot syndrome (HFS) most common in Arm B (49.5% versus 2.5% Arm A). Diarrhoea (Arm A: 0.4%, Arm B: 1.4%) and pulmonary embolism (Arm A: 0.7%, Arm B: 1.1%) were the most frequently reported SAEs. CONCLUSION: These findings are in-line with safety data for bevacizumab plus paclitaxel or capecitabine, reported in previous phase III trials.

Third consensus on medical treatment of metastatic breast cancer.

BACKGROUND: Treatment options for patients with metastatic breast cancer (MBC) include a rapidly expanding repertoire of medical, surgical and supportive care measures. DESIGN: To provide timely and evidence-based recommendations for the diagnostic workup and treatment of patients with MBC, an international expert panel reviewed and discussed the evidence available from clinical trials regarding diagnostic, therapeutic and supportive measures with emphasis on their impact on the quality of life and overall survival of patients with MBC. RESULTS: Evidence-based recommendations for the diagnostic workup, endocrine therapy, chemotherapy, use of targeted therapies and bisphosphonates, surgical treatment and supportive care measures in the management of patients with MBC were formulated. CONCLUSIONS: The present consensus manuscript updates evidence-based recommendations for state-of-the-art treatment of MBC depending on disease-associated and biological variables.

Second consensus on medical treatment of metastatic breast cancer.

The present consensus manuscript defines evidence-based recommendations for state-of-the-art treatment of metastatic breast cancer depending on disease-associated and biologic variables.

How to make the best use of limited resources in breast cancer treatment--experiences in Bosnia & Herzegovina.

Availability of effective treatment has been shown to have a profound, positive impact on survival of breast cancer patients. However, with passing of time treatment of breast cancer has become more complex and associated with increase of costs that puts an enormous burden on health care resources. In order to compare the costs and outcomes of different treatments, we have made our own assessment of costs of breast cancer treatment based on the existing situation in Bosnia & Herzegovina (B&H) and data available from the relevant literature. In B&H costs of breast cancer therapy constitute about one third of the total cost for all tumor types therapies, and this is proportional to the relative number of the treated patients. Prices of overall treatment vary predominantly according to the use of specific adjuvant chemotherapy (CT) and hormonal therapy (HT). FAC (5 fluorouracil/doxorubicin/cyclophosphamide/methotrexate/5 fluorouracil), higher doses of epirubicin in FE(100)C are twice as high compared with FAC. Inclusion of taxanes further increases costs (40-fold for AC[(doxorubicin/cyclophosphamide) + paclitaxel x 4]; 60-fold for TAC with docetaxel; 70-fold for dense-dose regimens in relation to FEC). Treatment with aromatase inhibitors is 11-13 times more expensive compared to tamoxifen. Therapy of metastatic disease is heterogeneous, and it is likely to prolong median survival by 14 months on average. Overall costs vary according to specific treatment modalities used. From CMF and FEC to trastuzumab and docexatel prices have increased 300 times. All health care systems have a limited budget, but wise use of health care resources is of special importance in countries in transition with evident weakness in economy. In the early breast cancer (EBC) setting, therapy should be individualised according to evidence-based data and respecting available resources. In metastatic disease (MBC) it should be based on risk factors, predictive factors, toxicity, preference of the patient herself and available resources, and weighted against effect on quality of life and treatment costs.

A phase II study of gemcitabine plus carboplatin in platinum-sensitive, recurrent ovarian carcinoma.

OBJECTIVES: Gemcitabine and carboplatin each have demonstrated effectiveness without increased neurotoxicity in pretreated patients with ovarian cancer. We evaluated the efficacy and safety of gemcitabine plus carboplatin in patients with recurrent ovarian cancer in a multicenter phase II study. METHODS: Women with histologically proven measurable or evaluable epithelial ovarian cancer (any FIGO) who relapsed > or =6 months after discontinuation of first-line, platinum-containing therapy received gemcitabine 1000 mg/m(2) on days 1 and 8 and carboplatin AUC 4 on day 1 (after gemcitabine) every 21 days for up to six cycles. RESULTS: Of the 40 enrolled/evaluable patients, 6 (15%) had complete response and 19 (47.5%) had partial response (PR), including one patient with PR in nonmeasurable disease (PRNM), for an overall response rate of 62.5% (95% CI, 45.8-77.3%). The median duration of response was 7.8 months (95% CI, 6.7-10.0), the median time to progressive disease was 9.6 months (95% CI, 8.5-11.0), and the median time to treatment failure was 9.3 months (95% CI, 8.2-10.4). The main grade 3/4 toxicities were neutropenia (78% of patients), leukopenia (30%), thrombocytopenia (18%), and anemia (15%); no grade 4 nonhematologic toxicities occurred, and grade 3 nonhematologic toxicities were mild. CONCLUSIONS: The combination of gemcitabine and carboplatin is active and feasible in platinum-sensitive patients with recurrent ovarian cancer. This regimen is undergoing further evaluation in a large phase III trial.

Randomized phase II study of induction chemotherapy with gemcitabine plus cisplatin followed by sequential radiotherapy versus radiotherapy alone in patients with stage III non-small cell lung cancer.

PURPOSE: This randomized phase II trial was conducted to compare the overall response rate (ORR) of gemcitabine plus cisplatin combination followed by sequential radiotherapy (RT) (arm A) versus RT alone (arm B) in chemonaive patients with stage IIIA or IIIB non-small cell lung cancer (NSCLC). Secondary objectives were to evaluate time to progressive disease (TTPD), overall survival, and treatment tolerability in both arms. PATIENTS AND METHODS: Eligible patients were required to have stage IIIA or stage IIIB NSCLC, no previous chemotherapy, ECOG performance status of 0-2, bidimensionally measurable disease, and age 18 to 75 years. Patients randomized in arm A were given 3 cycles of induction chemotherapy with gemcitabine 1250 mg/m(2) on days 1 and 8, plus cisplatin 80 mg/m(2) on day 1, every 21 days, followed by RT. In both arms, total dosage of RT was 63 Gy given in 34 fractions. Treatment continued until disease progression or unacceptable toxicity. RESULTS: Enrolled patients in both arms (30 in each arm) were well balanced for demographics and disease characteristics. The ORR, median TTPD and overall survival duration were 46.6/26.6%, 9.9/7.1 months and 12.5/10.0 months for arm A and arm B, respectively. The chemoradiation arm (arm A) was associated with significantly higher hematologic toxicities (anemia, neutropenia and thrombocytopenia) and nonhematologic toxicities (nausea, vomiting, paresthesias and alopecia). CONCLUSION: Sequential chemoradiation seems to be more effective than radiation alone, with acceptable toxicity profile. Confirmation phase III studies are warranted.

Adjuvant chemotherapy of breast cancer.

Breast cancer is the most common cancer and the second most common cause of cancer-related death in women. The last three decades have yielded marked progress in the diagnosis and management of breast cancer. Not only is the disease being detected at a much earlier stage, but the addition of systemic therapy has also improved survival. Cyclophosphamide (C), methotrexate (M) and 5-fluorouracil (F)(CMF) combination chemotherapy was among the first chemotherapy regimens found to prolong both disease-free survival (DFS) and overall survival (OS) when given in the adjuvant setting. The 2000 Oxford overview confirmed that anthracycline-based chemotherapy offers a survival advantage compared with CMF. Anthracycline-based therapies are better tolerated in terms of acute side effects but long-term sequels (cardiotoxicity, secondary leukaemia) are worrisome. It seems that more intensive three-drug regimens (FE[epirubicin](100)C, CEF, CA[adriamycin]F,) or the combination of E+CMF are more active in reducing the risk of relapse and death in breast cancer patients. The reported trials with taxanes demonstrated comparable reduction in the risk of recurrence and death, although administration of paclitaxel (T)-containing regimens appears to be most effective if administered on an every-2-week schedule with granulocyte colony-stimulating factor (G-CSF). The risk of febrile neutropenia is highest for the TAC regimen (~25%), although other trials have demonstrated that use of G-CSF will reduce this complication to about 3%.

[Oral complications of chemotherapy of malignant neoplasms]. / Oralne komplikacije hemoterapije malignih neoplazmi.

Function and integrity disorders of the oral cavity fall into the most frequent complication of the chemotherapy of leucemias, malignant lymphomas and solid tumors. Complications associated with cancer chemotherapy can be direct ones, resulting from the toxic action of antineoplastic agents on the proliferative lining of the mouth, or indirect, as a result of myelosuppression and immunosuppression. The most frequent oral complications associated with cancer chemotherapy are mucositis, infection and bleeding. The principles of prevention and management of oral complications during cancer chemotherapy are considered in this paper.