Safety and efficacy of addition of bevacizumab to oxaliplatin-based preoperative chemotherapy in colorectal cancer with liver metastasis- a single institution experience.

PURPOSE: To evaluate the safety and efficacy of the addition of bevacizumab to oxaliplatin-based preoperative chemotherapy in metastatic colorectal cancer (mCRC) patients. METHODS: Between August 2008 and December 2011, 51 patients with histologically documented CRC and liver metastases were treated with first-line oxaliplatin-based therapy plus bevacizumab: FOLFOX 4 (oxaliplatin, folinic acid and 5-FU) plus bevacizumab or OXFL mod.Mayo (folinic acid, oxaliplatin and 5-FU) plus bevacizumab. RESULTS: The mean patient age was 59.69+ 9.38 years (range 38-78) and 34 (66.67%) were male. Complete response (CR) was achieved in 7 (13.73%) patients, partial response (PR) in 29 (56. 86%) and stable disease (SD) in 6 (11.76%); progressive disease (PD) was registered in 9 (17.65%) patients. Disease control rate was 82.36% (42 patients). Liver resections were performed in 37 (72.55%) patients vs those without resection (p<0.01). The same regimen without bevacizumab was administered postoperatively to 18 (42. 86%) patients. The mean progression free survival (PFS) was 9.90±7.07 months (range 3-26) and was significantly longer in patients with postoperative therapy (p<0.001). Treatment-related toxicity appeared in 28 (54. 90%) patients vs those who did not (p<0.001) Independent of grade, nausea (19.61%), leucopenia (17.65%) and peripheral neuropathy (17.65%) were the most frequent toxicities. Chemotherapy was postponed in 9 (17.65%) patients due to grade 3-4 toxicities. The most frequent grade 3 or 4 toxicities were leucopenia (5.88%) and hypertension (3.92%). CONCLUSION: Bevacizumab plus oxaliplatin-based treatment is safe and efficient as preoperative treatment of mCRC with primarily unresectable liver metastases. Liver resection could offer a possibility for long-term survival in these patients.

Current and future anti-HER2 therapy in breast cancer.

The therapeutic strategy for breast cancer with the use of targeted drugs is, at present, mainly focused on coping with HER2. Currently, lapatinib and trastuzumab are in widespread use. Virtually all completed and in progress clinical trials have demonstrated a significant enhancement in the rate of pathologic complete response (pCR), the primary endpoint in these studies, in cases of patients with HER2-positive breast cancer that received trastuzumab in the neoadjuvant setting. Use of lapatinib in the neoadjuvant setting should be considered experimental. When a 12-month course of trastuzumab was added to adjuvant chemotherapy, the disease-free survival (DFS) was greater and the overall survival (OS) was also greater. Although trastuzumab is approved as single-agent therapy, most patients are treated with trastuzumab plus cytotoxic agents. Trastuzumab, administered as single agent, produces durable objective responses and is well tolerated by women with HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. Dual targeting approach with a combination of trastuzumab and lapatinib improved progression-free survival (PFS) as compared with lapatinib alone in patients with metastatic breast cancer who have not had a response to trastuzumab. The combination of pertuzumab plus trastuzumab plus docetaxel, as compared with placebo plus trastuzumab plus docetaxel, when used as first-line treatment for HER2-positive metastatic breast cancer, significantly prolonged PFS. Novel anti-HER2 targeted therapies are needed to utilise novel approaches to combat trastuzumab resistance.

The application of magnetic resonance imaging in preoperative evaluation of patients with endometrial carcinoma.

PURPOSE: The aim of this paper was to assess the usefulness of the preoperative application of magnetic resonance (MRI) imaging in patients with confirmed endometrial carcinoma. METHODS: This prospective study included 50 patients with endometrial cancer. MRI was used for preoperative disease staging and in planning the operative treatment. The parameters monitored by MRI were compared with the findings of curettage pathological examination. Estimated were the depth of myometrial invasion, the involvement of the cervix by the tumor, the presence of adnexal metastases and regional lymph nodes. Sensitivity, specificity, positive (PPV) and negative predictive value (NPV) of the MRI in relation to the aforementioned clinicopathological parameters were assessed. RESULTS: The presence of myometrial invasion was estimated with 100% specificity, 86% sensitivity, 100% PPV and 40% NPV. The estimation of the depth of myometrial invasion (>or<50%) was defined with 89% sensitivity, 54% specificity, 83% PPV and 60% NPV. MRI provided valuable data about cervical invasion (100% PPV for the presence of cervical invasion and 55% PPV for the depth of cervical invasion), thereby helping to decide on the kind of surgical intervention, the choice of approach (open or laparoscopic surgery) and the choice of the surgeon. CONCLUSION: MRI is useful and reliable in preoperative evaluation. The information obtained by MRI provides space and time for planning the treatment modality.

Concurrent chemoimmunotherapy: is it still the best option for the treatment of metastatic melanoma in patients with good performance status?

PURPOSE: To determine the efficacy, toxicity and survival of metastatic melanoma patients with Eastern Cooperative Oncology group good performance status (ECOG PS 0-1) receiving concurrent chemotherapy and immunotherapy. METHODS: From March 2003 to August 2008, 25 patients with metastatic melanoma were enrolled in the study. No patient had previously received chemotherapy or immunotherapy. Patients with ECOG PS 0-1 were treated with cisplatin+vinblastine+DTIC (CVD) and interferon-A2a (IFN-a). RESULTS: Response rate was 11/25 (44%): complete response (CR) 2, partial response (PR) 9, stable disease (SD) 11, progressive disease (PD) 3. Adverse effects were mild. The most common toxicities were nausea, vomiting and fever. Grade 3 and 4 toxicity was more common in hematologic parameters. No treatment-related deaths occurred. The median overall survival (OS) was 14 months and time to progression 8.0 months. CONCLUSION: Concomitant chemoimmunotherapy appeared to be a beneficial option for metastatic melanoma patients with good PS. Therapeutic approaches with less toxicity and regimens that could improve OS are still highly desired in the treatment of advanced malignant melanoma.

Therapy of stage IV B anaplastic thyroid carcinoma: single institution experience.

PURPOSE: To evaluate the efficacy of radiotherapy and chemotherapy in stage IV B anaplastic thyroid carcinoma (ATC). PATIENTS AND METHODS: From 1997 to 2007, 16 inoperable patients (12 females, 4 males, median age 60 years, range 27-71) with pathologically confirmed ATC without distant metastases (UICC stage IV B) were treated with radiotherapy and chemotherapy at our Institution. Five patients had Eastern Cooperative Oncology Group (ECOG) performance status 1, and 11 ECOG 2. All patients received the planned radiotherapy tumor dose of 60 Gy. Radiotherapy was followed by chemotherapy with doxorubicin 60 mg/m(2) and cisplatin 40 mg/m(2) every 3 weeks. The primary study endpoint was response rate (RR) and secondary endpoints were toxicity and overall survival (OS). RESULTS: Only one patient achieved complete response (CR: 6.25%, 95% CI: 0-35) and 3 patients (18.75%, 95% CI: 4-46) partial response (PR), for an overall response rate (ORR) of 25% (95% CI: 7-55). No toxic deaths occurred and no grade 4 adverse events were registered after radiotherapy. Grade 4 toxicity was seen in 3 patients (18.75%, 95% CI: 4- 46) after chemotherapy. Mean patient OS was 12.33 months (95% CI: 9.09-15.56) and median OS 11.0 months (95% CI: 8.56-13.44). CONCLUSION: Radiotherapy and chemotherapy of stage IV B anaplastic thyroid carcinoma are well tolerated. Although the clinical benefit was 50%, survival rates remain low with OS of no more than 2 years.

Chemotherapy in carcinomas of unknown primary site.

PURPOSE: Carcinomas of unknown primary site (CUPS) are highly malignant diseases with a usually ominous prognosis. We report on the efficacy of chemotherapy in the treatment and survival of patients with CUPS. PATIENTS AND METHODS: The study involved 63 patients with metastatic CUPS. Following routine light microscopy, the histological findings were classified into 3 groups: squamous cell carcinoma - 8 patients; adenocarcinoma - 33 patients; and undifferentiated carcinoma - 22 patients. Combination chemotherapy with doxorubicin 50 mg/m(2) (day 1), cisplatin 60 mg/m(2) (day 1), and etoposide 120 mg/m(2)/day (days 1-3) every 3 weeks was administered to 32 patients (20 females and 12 males), aged 29-70 years (median 54 years) who met the inclusion criteria. All patients with stable disease (SD), partial response (PR) or complete response (CR) received 6 cycles of chemotherapy. RESULTS: CR was achieved in 3 (9.4%), PR in 12 (37.5%), and SD in 10 (31.2%) patients. Seven (21.9%) patients had progressive disease (PD). The overall response rate (RR) was 46.9% (15/32) and the median response duration of CR+PR was 11 months (range 4-43(+) months). The overall survival (OS) of patients treated with chemotherapy (n=32; 50.8%) was better compared with the OS of those not receiving chemotherapy (n=31; 49.2%/; p <0.01). Also the 2-year survival of patients with chemotherapy (40%) and without chemotherapy (0%) implies potential curability in a specific subset of these patients. CONCLUSION: The usage of the aforementioned doses and chemotherapy scheme appears to improve the outcome of patients with carcinoma of unknown primary site.

Sensitivity, specificity, positive and negative predictive value of serum S-100 beta protein in patients with malignant melanoma.

PURPOSE: To establish the sensitivity, specificity, positive (PPV) and negative predictive value (NPV) of serum S-100 beta protein (sSB) in patients with malignant melanoma (MM), based on its concentration in the peripheral blood and the likelihood ratio (LR) for the whole group of patients with MM, as well as for each separate clinical stage. PATIENTS AND METHODS: sSB was determined immunoluminometrically in 172 patients with histologically confirmed MM. Sera from 64 healthy subjects were used as controls. RESULTS: Increased values of sSB were detected in 65 out of 172 patients with MM, and in 5 cases among healthy subjects. Sensitivity, specificity, PPV and NPV were 38%, 92%, 93% and 35%, respectively. In stage I 1/29 patients had increased values of sSB, in stage II 3/34, in stage III 13/47 and in stage IV 48/62 patients. Sensitivity, specificity, PPV and NPV for stage I were 3%, 92%, 17% and 68%, respectively/ for stage II 9%, 92%, 37% and 65%, respectively; for stage III 28%, 92%, 72% and 63%, respectively; and for stage IV 77%, 92%, 91%, and 81%, respectively. The LR for sSB values of >13 mug/l was 5 for the whole group of patients with MM, 0.4 for stage I, 1 for stage II, 3 for stage III and 10 for stage IV. CONCLUSION: Based on our results we conclude that sSB is a reliable serum marker for the diagnosis of stage IV MM.

Adjuvant chemotherapy of premenopausal breast cancer patients and patients under 35 years of age.

Micrometastases in patients with primary breast cancer are the rationale for adjuvant systemic treatment. The Early Breast Cancer Trialists' Collaborative Group (EBCTCG) sequential studies have shown that adjuvant systemic therapy decreases recurrence and prolongs survival. According to tumour and patient-related prognostic factors, the risk for relapse could be evaluated. If the risk for relapse is over 10% for 10 years, adjuvant systemic therapy is indicated. Adjuvant chemotherapy is associated with a greater 15-year absolute reduction in death in premenopausal than in postmenopausal patients. Anthracycline- based regimens have demonstrated superiority over classic cyclophoshamide, methotrexate and 5- fluorouracil (CMF) combination chemotherapy, and the role of taxanes is questionable. Timing and duration of adjuvant chemotherapy plays an important role in its individualization. The need for tailored treatments in premenopausal patients is most pronounced in women under 35 years of age at diagnosis.

Simultaneous or sequential chemotherapy for locally advanced breast cancer.

Chemotherapy of breast cancer is still an area of intensive research. Based on mathematical model of tumor cell growth kinetics, a novel concept of chemotherapy in breast cancer was launched which implies dose-densification of chemotherapy through the use of sequential non crossresistant single agents or regimens. The relative infrequency of locally advanced breast cancer (LABC) has limited the speed of clinical progress in this area. The introduction of primary (neoadjuvant) systemic chemotherapy (PSCT), however, improved the outcome of patients with LABC. The first data concerning neoadjuvant sequential chemotherapy were related to primary operable breast cancer. Many studies, using the two most active classes of cytotoxic drugs, anthracyclines and taxanes, in primary breast cancer, showed that sequential PSCT was superior to simultaneous combination chemotherapy in terms of enhancing the rates of patients rendering suitable for breast-conserving (BC) treatment. There are few trials dealing with sequential PSCT in LABC. In the majority of them sequential dose-dense PSCT was administered because the rapid delivery of the most active cytotoxic drugs (anthracyclines and taxanes) is necessary to achieve reduction of the size of the primary tumor, to increase the possibility of BC treatment and to eliminate occult distant micrometastases, contributing thus to possible prolongation of survival. This article summarises recent data concerning sequential PSCT in LABC in order to evaluate its possible use in clinical practice.