Handan Onur

Cisplatin plus oral etoposide (EoP) combination is more effective than paclitaxel in patients with advanced breast cancer pretreated with anthracyclines: a randomised phase III trial of Turkish Oncology Group

Our objective was to determine whether oral etoposide and cisplatin combination (EoP) is superior to paclitaxel in the treatment of advanced breast cancer (ABC) patients pretreated with anthracyclines. From December 1997 to August 2003, 201 patients were randomised, 100 to EoP and 101 to paclitaxel arms. Four patients in each arm were ineligible. The doses of etoposide and cisplatin were 50 mg p.o. twice a day for 7 days and 70 mg m−2 intravenously (i.v.) on day 1, respectively, and it was 175 mg m−2 on day 1 for paclitaxel. Both treatments were repeated every 3 weeks. A median of four cycles of study treatment was given in both arms. The response rate obtained in the EoP arm was significantly higher (36.3 vs 22.2%; P=0.038). Median response duration was longer for the EoP arm (7 vs 4 months) (P=0.132). Also, time to progression was significantly in favour of the EoP arm (5.5 vs 3.9 months; P=0.003). Median overall survival was again significantly longer in the EoP arm (14 vs 9.5 months; P=0.039). Toxicity profile of both groups was similar. Two patients in each arm were lost due to febrile neutropenia. The observed activity and acceptable toxicity of EoP endorses the employment of this combination in the treatment of ABC following anthracyclines.

Phase II study of lapatinib in combination with vinorelbine in patients with HER2 positive recurrent or metastatic breast cancer: A multicentric Turkish Oncology Group (TOG) trial

BACKGROUND The aim of this explorative phase II study was to evaluate the activity and safety of lapatinib in combination with intravenous vinorelbine in women with HER2 positive metastatic or recurrent breast cancer. METHODS Twenty-nine patients were enrolled. The primary objectives were response and clinical benefit (CB) rates, secondary objectives were toxicity, response duration and progression free survival. Patients received 1250 mg oral lapatinib continuously once daily and intravenous vinorelbine 20-25 mg/m(2) on days 1 and 8, every 3 weeks. RESULTS Although 25 patients were evaluable for response, according to intend to treat analysis of 28 patients; 14% had confirmed partial response (PR) and 36% had stable disease more than 24 weeks with a CB rate of 50%. Sixty four percent of the patients suffered from grade 3-4 hematologic and 18% from grade 3 extra-hematologic toxicities. CONCLUSION The results of this trial provide evidence to further investigate the potential of this combination for patients unsuitable for trastuzumab or who become refractory to trastuzumab.

The symptomatic benefit (the clinical benefit response) from the second-line chemotherapy in patients with advanced gastric adenocarcinoma

There are few reports on use of symptomatic benefits as an alternative or adjunctive for the assessment of objective response in chemotherapy of the advanced cancer. This study is performed to assess the symptomatic benefits (the clinical benefit response), in addition to the efficacy and toxicity of cisplatin plus infusional 5-fluorouracil (5-FU) combination as second-line therapy in patients with advanced gastric cancer. Fifty-eight advanced gastric cancer patients with previous chemotherapy were enrolled into the study. Cisplatin 20 mg/m(2) was given for 5 days, and 5-FU was given 1000 mg/m(2) as 20 h continuous infusion for 5 days, repeated every 28 days. The overall objective response rate was 11.3%, and overall tumour control rate was 33.9%. The clinical benefit response, in terms of weight gain, reduction in analgesic consumption and the improvement in performance status observed in 12 patients [six patients with partial response (PR) and six patients with stable disease (SD)] (22.6%), while the rates of the clinical benefit response in patients with PR and with SD were 100% and 50% respectively. Cisplatin plus infusional 5-FU combination seems to improve disease-related symptoms (clinical benefit response) of patients with advanced gastric cancer, even in patients without objective response.

Prospective randomized comparison of morning versus night daily single subcutaneous administration of granulocyte-macrophage-colony stimulating factor in patients with soft tissue or bone sarcoma.

Hematopoietic growth factors (HGFs) have been used to reduce the neutropenic complications of cytotoxic chemotherapy so that higher doses may be given. The authors have previously shown that endogenous serum granulocyte‐colony stimulating factor (G‐CSF) and granulocyte‐macrophage–colony stimulating factor (GM‐CSF) levels at night (p.m.) were significantly higher than those in the morning (a.m.).

The Outcome of Patients with Triple Negative Breast Cancer: The Turkish Oncology Group Experience

OBJECTIVE Triple negative breast cancer (TNBC) is generally considered as a poorer prognostic subgroup, with propensity for earlier relapse and visceral involvement. The aim of this study is to evaluate the outcome of non-metastatic TNBC patients from different centers in Turkey and identify clinical and pathologic variables that may effect survival. MATERIALS AND METHODS Between 1993-2007, from five different centers in Turkey, 316 nonmetastatic triple negative breast cancer patients were identified with follow-up of at least 12 months. The data was collected retrospectively from patient charts. The prognostic impact of several clinical variables were evaluated by the Kaplan-Meier and Cox multivariate anayses. RESULTS Mean age at diagnosis was 49 years (range: 24-82). The majority of the patient group had invasive ductal carcinoma (n: 260, 82.3%) and stage II disease (n: 164; 51.9%). Majority of the patients (87.7%) received adjuvant chemotherapy. 5 year overall survival (OS) and disease-free survival (DFS) rates were 84.6% and 71.6%, respectively. Univariate analysis revealed locally advanced disease (p: 0.001), advanced pathological stage (p: 0.021), larger tumor size (T1&T2 vs T3&T4) (p<0.001), nodal positivity (p: 0.006), and extensive nodal involvement (p<0.001) as significant factors for DFS; whereas, advanced pathological stage (p: 0.017), extensive nodal involvement (p<0.001) and larger tumor size (p: 0,001) and presence of breast cancer-affected member in the family (p=0.05) were identified as prognostic factors with an impact on OS. Multivariate analysis revealed larger tumor size (T3&T4 vs T1&T2) and presence of lymph node metastases (node-positive vs node-negative) as significant independent prognostic factors for DFS (Hazard ratio (HR): 3.03, 95% CI: 1.71-5.35, p<0.001 and HR: 1.77, 95% CI: 1.05-3.0, p=0.03, respectively). Higher tumor stage was the only independent factor affecting overall survival (HR: 2.81; 95% CI, 1.27-6.22, p=0.01). CONCLUSION The outcome of patients with TNBC in this cohort is comparable to other studies including TNBC patients. Tumor size and presence of lymph node metastasis are the major independent factors that have effect on DFS, however higher tumor stage was the only negative prognostic factor for OS.

Adjuvant oral etoposide plus cisplatin (EoP) following sequential doxorubicin/ cyclophosphamide (AC) and docetaxel (T) in early breast cancer patients with 4 or more positive lymph nodes (10 years follow-up)

BACKGROUND AND OBJECTIVES Previous reports suggest that including cisplatin plus etoposide in the adjuvant treatment may improve the outcomes in patients with early breast cancer. PATIENTS AND METHODS Forty-one patients with early breast cancer and 4 or more positive lymph nodes were treated with 3 cycles of EoP (oral etoposide plus cisplatin) in addition to 3 cycles of AC (doxorubicin plus cyclophosphamide) and 3 cycles of T (docetaxel) (Group 1). Toxicity and survival results were compared to those with similar disease characteristics who were treated with 4 cycles of AC plus 4 cycles of T (Group 2) during the same period. RESULTS There were no long-term side effects related to EoP. While median disease-free and overall survivals were not reached in Group 1, they were 107 ± 13 (p = 0.387) months and 123 ± 5 months (p = 0.618) in Group 2. Likewise 10-year disease-free survivals (DFS) were 59.3% and 44.7% respectively. CONCLUSIONS The trend towards improvement in survival with adjuvant AC + T + EoP when compared to AC + T needs to be studied in randomized trial.

The Effects of Chronomodulated Therapy with 5-Fluorouracil (5-Fu) and Folinic Acid (Fa) on the Toxicity and Quality of Life in Patients with Advanced Gastric Cancer

This study was designed to assess the tolerability of chronomodulated infusion chemotherapy, individualized by the rhythm of peripheral blood cells. Twenty patients with metastatic gastric cancer were randomized to chronotherapy or day-time arms of 5-fluorouracil (FU) (600 mg/m2, 8 h inf.d1–5) and folinic acid (FA) (20 mg/m2, iv, d1–5) in the first cycle and crossed-over to the other arm in the following cycles. Ten of 18 evaluable patients were assigned to chronotherapy arm and eight to day-time in the first cycle. Although there was no significant difference between two arms on enrollment, chronotherapy arm yielded an improvement of 45% of QLQ-C30 scores (p = 0.021) and the day-time arm had 11% improvement (p = 0.575). After the crossing-over, chronotherapy arm, again, had a significant improvement in QLQ-C30 scores, compared to the day-time arm (14% vs. −18%, p = 0.001, respectively). Mucositis/diarrhea was significantly higher in the day-time arm compared to chronotherapy arm (p = 0.015). In conclusion, chronomodulated infusion of 5-FU might improve the quality of life.

Immunohistochemical HER2 Status Evaluation in Breast Cancer Pathology Samples: A Multicenter, Parallel-Design Concordance Study

Objective As patients with increased human epidermal growth factor receptor (HER2) overexpression are more likely to benefit from trastuzumab treatment, the accuracy of HER2 receptor status in breast cancer patients is significant for appropriate disease management. However, this assessment is not harmonized and results may be highly variable between centers. The aim of this study was to investigate the degree of interlaboratory variability in the results of HER2 expression reported by 5 participating centers and to assess the concordance between these centers and a reference laboratory.Materials and Methods: A total of 30 breast cancer samples were tested and scored for HER2 expression using immunohistochemical method in 5 centers from Turkey and in a reference laboratory from Netherlands (Academic Medical Center, Amsterdam). All the participating centers had an experience of more than 10 years regarding the HER2 testing. The results were compared both among the centers and with the reference laboratory. Results When the concordance of participating centers and the reference laboratory was evaluated regarding negative (0-1+), equivocal 2(+) and positive 3(+) classification of HER2 immunostaining, the highest concordance was found in Center-A, and the lowest in Center-C (Kendalls tau-b concordance coefficient 0.911 and 0.724, respectively). The concordance of the centers with reference laboratory was 80.0% both in equivocal and positive samples, while it increased up to 91.8% in negative samples. Conclusions This study showed that in general there is sufficiently good agreement between the reference laboratory and the participating centers for immunohistochemical HER2 assessment.

Diagnostic serum vitamin D level is not a reliable prognostic factor for resectable breast cancer

AIM There are inconsistent results about the effects of vitamin D level on breast cancer prognosis. We aimed to investigate the effect of vitamin D levels on the prognosis of resectable breast cancer in a patient group with highly different clothing styles. PATIENTS & METHODS A total of 186 breast cancer patients were enrolled in the study. RESULTS Vitamin D level was sufficient, insufficient and deficient in 17.2, 52.2 and 30.6% of patients, respectively. There was a significant relationship between clothing style and serum 25 (OH) D levels. We could not establish any relation between vitamin D level and tumor characteristics or survival. CONCLUSION Vitamin D supplementation can be more important than diagnostic serum vitamin D level on prognosis of breast cancer.