Pertuzumab, trastuzumab and taxane-based treatment for visceral organ metastatic, trastuzumab-naïve breast cancer: real-life practice outcomes.

PURPOSE: In this study, we aimed to describe the real-life practice outcomes of pertuzumab-trastuzumab-taxane (PTT) combination in visceral organ metastatic, trastuzumab-naive breast cancer (BC) patients. METHODS: This study was conducted by Turkish Oncology Group and included 317 patients' data from 36 centers. RESULTS: Median age was 51 (22-82). Median PFS was 28.5 months, while median OS was 40.3 months. Patients with brain metastases (n: 13, 4.1%) had worse PFS (16.8 m vs. 28.5 m; p = 0.002) and OS (26.7 m vs. 40.3 m; p = 0.009). Patients older than 65 years of age (n: 42, 13.2%) had significantly lower OS results (19.8 m vs. 40.3 m; p = 0.01). Two hundred sixty-eight patients (86.7%) received docetaxel while 37 patients (11.7%) received paclitaxel. PFS and OS were similar between taxane groups. In eight patients (2.5%), 5-40% ejection fraction decrement from baseline was detected without any clinical sign of heart failure. CONCLUSIONS: Our RLP trial included only visceral metastatic, trastuzumab-naïve BC patients including cases with brain involvement who received PTT combination in the first-line treatment. Regardless of negative prognostic characteristics, our results are in parallel with pivotal trial. Further strategies for brain metastasis should be developed to improve outcomes despite encouraging results with PTT treatment. Taxane selection can be personalized and endocrine maintenance may further improve outcomes after taxanes were discontinued. To our knowledge, this is the largest scale real-life clinical practice study of pertuzumab-trastuzumab-taxane therapy to date.

Assessment of Palliative Care in Lung Cancer in Turkey.

OBJECTIVE: To investigate the symptoms of lung cancer in Turkey and to evaluate approaches to alleviate these symptoms. SUBJECTS AND METHODS: This study included 1,245 lung cancer patients from 26 centers in Turkey. Demographic characteristics as well as information regarding the disease and treatments were obtained from medical records and patient interviews. Symptoms were evaluated using the Edmonton Symptom Assessment Scale (ESAS) and were graded on a scale between 0 and 10 points. Data were compared using the χ2, Student t, and Mann-Whitney U tests. Potential predictors of symptoms were analyzed using logistic regression analysis. RESULTS: The most common symptom was tiredness (n = 1,002; 82.1%), followed by dyspnea (n = 845; 69.3%), appetite loss (n = 801; 65.7%), pain (n = 798; 65.4%), drowsiness (n = 742; 60.8%), anxiety (n = 704; 57.7%), depression (n = 623; 51.1%), and nausea (n = 557; 45.5%). Of the 1,245 patients, 590 (48.4%) had difficulty in initiating or maintaining sleep. The symptoms were more severe in stages III and IV. Logistic regression analysis indicated a clear association between demographic characteristics and symptom distress, as well as between symptom distress (except nausea) and well-being. Overall, 804 (65.4%) patients used analgesics, 630 (51.5%) received treatment for dyspnea, 242 (19.8%) used enteral/parenteral nutrition, 132 (10.8%) used appetite stimulants, and 129 (10.6%) used anxiolytics/antidepressants. Of the 799 patients who received analgesics, 173 (21.7%) reported that their symptoms were under control, and also those on other various treatment modalities (dyspnea: 78/627 [12.4%], appetite stimulant: 25/132 [18.9%], and anxiolytics/antidepressants: 25/129 [19.4%]) reported that their symptoms were controlled. CONCLUSION: In this study, the symptoms progressed and became more severe in the advanced stages of lung cancer, and palliative treatment was insufficient in most of the patients in Turkey.

A case of Kikuchi-Fujimoto disease misdiagnosed as Hodgkin's lymphoma: the importance of second opinion.

Kikuchi-Fujimoto disease (KFD), a rare clinicopathological entity, is a benign and self-limiting disease. It was first described in 1972 by Kikuchi and Fujimoto in Japan independently. KFD is prevalent in Asia, although it may be seen in wide geographical areas, including Turkey. It mainly affects young women. Cervical lymphadenopathy is the most prominent sign and should be differentiated from lymphoproliferative, autoimmune, and infectious diseases. We report on a 30-year-old female patient who was referred to our medical oncology unit for chemotherapy and/or radiotherapy with diagnosis of Hodgkin's lymphoma. Ultimately her diagnosis was corrected as KFD after second opinion of the pathology specimens. We herein provide a brief review about KFD and the importance of second opinion of the pathology specimens.

Prolonged interval in prophylactic heparin flushing for maintenance of subcutaneous implanted port care in patients with cancer.

The long-term use of subcutaneous implanted ports for chemotherapy in cancer patients has been associated with the occurrence of thrombosis and infection. In this study, we compared the safety and efficacy of administration of 1000 U of heparin flushes in prolonged interval (every 6 weeks) with standard dose and schedule (500 U every 4 weeks) for port-related infections and thrombosis during periods of non-use. Data were collected retrospectively from patients treated for various cancer types (matched as 2:1 for age, gender, stage of the disease). Patients who had diseases that could cause thrombosis or bleeding in their past medical history, or were taking oral anticoagulants, or had contraindications for heparin usage were excluded. After completing their chemotherapy, 59 patients received prolonged interval, while 30 patients received standard schedule. All patients were followed for at least 1 year. No clinically documented port-related infection or thrombosis has been found in both groups. Also, none of the devices was removed during this time. Prophylactic flushing of central venous ports with 1000 U of heparin in every 6 weeks might be a safe, easy, cheaper, comfortable and effective alternative to standard dose and schedule for preventing thrombosis and infections.

Toxicity and feasibility analysis for cisplatin-based concomitant chemoradiotherapy in locally advanced nasopharyngeal carcinoma.

PURPOSE: To assess the side effects of cisplatin-based concurrent chemoradiotherapy (CRT) for locally advanced nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: From 2001 through 2007, 34 (27 males; 7 females) patients received a median of 70 Gy curative radiotherapy (RT) with conventional fractionation. Twenty-one (62%) patients received induction chemotherapy (CT): 8 of them received 2 courses of cisplatin (75 mg/m(2), day 1) and 5-fluorouracil (5-FU) (750 mg/m(2), days 1-5) every 3 weeks and 13 patients received 3 courses of cisplatin (75 mg/m(2), day 1) and docetaxel (75 mg/m(2), day 1) every 3 weeks. Concomitant cisplatin was administered either 40 mg/m(2) weekly (n=8) or 75-80 mg/m(2) every 3 weeks (n=26) during RT. Median Karnofsky performance status (KPS) prior to RT was 80 (range 70-90). Patient, disease and treatment-related factors were analysed in relation to termination of concurrent CT. RESULTS: Concurrent CT was administered to 13 (38.2%) patients without cisplatin termination, whereas 10 (29.4%) patients received 2 cycles of the 3-weekly schedule. Grade 3 oral mucositis (47.1%), grade 2-3 weight loss (44.2%) and grade 2 fatigue (44.1%) were the most frequently dose-limiting side effects during concurrent therapy. The rate of receiving cisplatin cycles as planned was 85% for patients with KPS >80, whilst it was 15% only for patients with KPS < or = 80 (p=0.006). None of the patients suffering of grade 2 fatigue could complete all cycles compared to 68% of patients with < grade 2 fatigue who completed all cycles (p <0.001). The severity of mucositis was significantly related to initial haemoglobin level (p=0.02) and weight loss during RT (p=0.04). Median follow-up was 20 months (range 5-65). Three-year locoregional relapse free (LRRFS), disease free (DFS) and overall survival (OS) rates were 79.3%, 68.8% and 79.2%, respectively. CONCLUSION: Concurrent administration of CT during RT reveals better outcome but requires careful consideration for toxicity. Initial performance status prior to CRT might be a predictor for unplanned CT stopping due to side effects.

Concomitant administration of uracil-tegafur and leucovorin during adjuvant radiotherapy for locally advanced rectal cancer.

PURPOSE: We report the feasibility and toxicity profile, and the impact on local control, disease-free survival and overall survival rates of our study which consisted of postoperative concurrent chemoradiotherapy, followed by adjuvant chemotherapy using uracil-tegafur (UFT)/leukovorin (LV) in locally advanced rectal cancer patients. PATIENTS AND METHODS: Thirty-one patients operated for rectal adenocarcinoma (pT3/4 or N+) were enrolled onto the study. Twenty-three patients were males and 8 females with median age 62 years (range 21-85). Radiotherapy (RT) to the pelvis with conformal technique and individual blocks was delivered within 8 weeks following surgery. Total RT dose was 50.4 Gy and was given in a conventional single fraction of 1.8 Gy per day. Chemotherapy was administered concomitantly and consisted of UFT (300 mg/m(2)/day) and LV (30 mg/day) during RT-days. Following chemoradiotherapy, chemotherapy alone was administered for 4 cycles in the same dose for 28 days every 35 days. RESULTS: No lethal toxicity occurred. All patients completed the scheduled RT. Concurrent chemotherapy continued in 22 (70.9%) patients until the end of RT. Seventeen (54.8%) patients completed the whole concurrent chemoradiotherapy and adjuvant chemotherapy as planned. No grade 3-4 stomatitis/mucositis or haematological toxicities were observed during the whole treatment period. During concomitant therapy grade 1-2 toxicities were: nausea/vomiting 60%, dyspepsia/gastric pain 39%, diarrhea 39% and dysuria 10%, whereas grade 3 nausea and diarrhea occurred in 6% and 19%, respectively. Median follow-up was 22 months. Two-year local control, disease-free survival and overall survival rates were 96.3%, 72.3% and 83.2%, respectively. CONCLUSION: The acute toxicity profile of UFT/LV, local control, disease-free survival and overall survival in the concurrent chemoradiotherapy setting for operated, locally advanced rectal cancer seem comparable with the standard 5-fluorouracil (5-FU)-based therapies.

HPV DNA frequency and subset analysis in human breast cancer patients' normal and tumoral tissue samples.

Viruses are known to be associated with human malignancies, e.g., Epstein-Barr virus, human papillomavirus (HPV) and human T-cell leukemia virus type I. We conducted a prospective study to define the role of HPV in breast cancer. The malignant and normal breast tissue samples of 50 consecutive breast cancer patients were obtained postoperatively. DNA extracted from all tissues was amplified with the polymerase chain reaction using HPV primers. HPV 11, 16, 18, 33 subtypes were searched in HPV-DNA positive samples. Thirty-seven samples (74%) of tumoral breast tissue expressed HPV-DNA, 16 normal breast tissue samples (32%) were positive as well. There was a significant difference in HPV-DNA positivity between normal and tumoral breast tissue samples. HPV 18 was detected in 20 of the HPV-DNA positive tumoral tissue (54.4%) and in 9 of the HPV-DNA positive normal tissue (56.3%). HPV-33 also was detected in 35 (94.6 %) of the HPV-DNA positive tumoral tissue and in 14 (87.5 %) of the HPV-DNA positive normal tissue samples. HPV DNA was significantly associated with breast tumor tissue compared to normal breast tissue. Additional studies looking at HPV and HPV subtypes are needed to clarify the etiological role of the HPV in breast cancer.

Outcome of rectal and sigmoid carcinoma patients receiving adjuvant chemoradiotherapy in Marmara University Hospital.

Adjuvant chemoradiotherapy is the standard treatment in resected stage II/III rectosigmoid carcinoma. We report a retrospective analysis of 33 patients who received adjuvant chemoradiotherapy. Patients received 5-fluorouracil (375mg/m2/day x 5days) and calcium leucovorin (20mg/m2/day x 5days), q4weeks, two courses before and two courses after radiotherapy. The 5-fluorouracil dose was reduced to 225mg/m2/day given continuously as protracted short-term infusion on the first and last 3 days during radiotherapy. Radiotherapy was started at 7th week and 45-50.4 Gy was given to pelvic region. Median age was 63 years. Median follow-up was 38 months starting from the operation date. Four-year local and distant control rates were 78% and 69%, respectively. Four-year disease-free survival and overall survival were 60% and 62%, respectively. Protracted short-term infusion of 5-fluorouracil during pelvic irradiation is a safe treatment modality. Further studies are needed to improve the local control of high-risk rectal and sigmoid carcinomas.