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.

Erectile dysfunction in testicular cancer patients treated with chemotherapy.

Information on male potency in testicular cancer (TC) patients treated with chemotherapy is insufficient. We aimed to assess the levels of depression and anxiety symptoms, sexual function and gonodotrophins. Participants (n = 27) were identified and recruited from the genitourinary services of two medical centres, one in Inonu University and the other in the Firat University. All patients are TC patients treated with chemotherapy after unilateral orchiectomy. Participants completed follow-up assessments after the completion of the chemotherapy regimen. Serum luteinising hormone, follicle-stimulating hormone and testosterone levels were determined after blood samples had been taken in the morning after an overnight fast. International Index of Erectile Function (IIEF-15) was also used to evaluate erectile dysfunction (ED) score. Beck Depression and Beck Anxiety Scale were used to assess psychological symptoms. The findings indicated that men treated with chemotherapy had significantly different IIEF-15 and Beck Anxiety scores compared with men who did not receive chemotherapy. But no statistically significant difference was determined in the serum gonodotrophin levels and depression score between the two groups. It is concluded that patients with TC undergoing chemotherapy have greater risk than normal men for ED, independently of the gonodotrophin's level.

Malignancies after rituximab treatment: just coincidence or more?

PURPOSE: Rituximab has been successfully used in the treatment of B-cell non-Hodgkin's lymphoma (NHL) and some autoimmune diseases nearly for a decade. Several other malignancies and CD20-negative lymphomas have been reported in the literature after rituximab treatment. We aimed to investigate whether there is an association between rituximab treatment and the development of second malignancies. METHODS: A detailed search in English language literature on reports about rituximab treatment and secondary malignancies was made through Medline. The papers were reviewed and the cases were summarized according to secondary tumor types, intervals between rituximab treatment and second malignancy occurrence, indications for rituximab treatment and cytotoxic chemotherapy administration. RESULTS: There were 26 previously reported cases of CD20-negative lymphoma and solid tumors after rituximab treatment. The median age of these cases was 62 years (range 34-80). The median time period from the initiation of rituximab treatment to diagnosis of second malignancies was 5 months (range 1-40). The most frequently reported solid tumors were skin tumors (squamous cell carcinoma and Merkel cell carcinoma) (n=7; 27%), CD20-negative lymphomas (n=5; 20%), Kaposi sarcoma (n=4; 15%), and others (n=10; 38%). CONCLUSION: Association between rituximab and subsequent development of second malignancies might be a coincidence. However, we suggest close monitoring for second malignancies, particularly skin tumors, in patients treated with rituximab. This issue should be evaluated in further studies.

Platelet size has diagnostic predictive value for bone marrow metastasis in patients with solid tumors.

Though not very common, solid tumor involvement of the bone marrow (BM) may have serious consequences. Recent studies have shown that mean platelet volume (MPV) is a good indicator for BM disease in the differential diagnosis of thrombocytopenia. We investigated the significance of MPV in the diagnosis of BM metastasis in patients with solid tumors. Patients with histologically-verified solid tumors for whom BM biopsy specimens were available (n = 121) and healthy controls (n = 62) were included in this retrospective study. A total of 183 individuals were analyzed. Of the patients, 61 had a diagnosis of BM metastasis (Group A), 60 did not have BM metastasis (Group B). Group B and C (healthy controls) constituted the control group without BM metastasis (n = 122). The mean MPV was 7.0 +/- 0.8 fl in patients with BM metastasis and 8.4 fl in the control group (P < 0.001). A cut-off point of <7.4 fl was found to have significant predictive value according to receiver-operating characteristics curve analysis. This cut-off point had 85% positive predictive value and 90% negative predictive value in the diagnosis of BM metastasis (odds ratio: 53; 95% confidence interval: 20-135), and a sensitivity of 82.7% and specificity of 89.6%. MPV can be used as a reliable marker to guide the clinician as to the likely presence or absence of BM metastasis in patients with solid tumors.

Differential alteration of drug-metabolizing enzyme activities after cyclophosphamide/adriamycin administration in breast cancer patients.

Cyclophosphamide (CPA) and adriamycin (ADR) are widely used drugs for cancer chemotherapy. It has been reported that CPA and ADR singly or in combination could alter activities of a variety of drug-metabolizing enzymes in animals via multiple mechanisms. However, the effects of CPA/ADR on drug metabolism are largely unknown in human beings. Losartan metabolism has been suggested as a marker for determination of CYP2C9 activity. Caffeine is a commonly used probe to assess the metabolic activities of CYP1A2, CYP2A6, N-acetyltransferase 2 (NAT2) and xanthine oxidase (XO). The present study was designed to analyze the effects of CPA/ADR on these drug-metabolizing enzymes by using losartan and caffeine as probe drugs. A single oral dose of 25 mg losartan and a cup of instant coffee was given to 15 breast cancer patients on three occasions (before, and 2-4 h and 3 weeks after the adjuvant CPA/ADR chemotherapy [600 mg CPA/m2/day, 60 mg ADR/m2/day]). Losartan, caffeine and their metabolites were analyzed by using high-pressure liquid chromatography. When compared with baseline, CYP1A2 activity was increased by 20% and CYP2C9 activity was decreased by 315% 3 weeks after the administration of CPA/ADR chemotherapy (p = 0.05). The chemotherapy did not change the activities of CYP2A6, NAT2 or XO. CPA/ADR treatment caused a differential effect on drug-metabolizing enzyme activities, and this may contribute to predicting the efficacy and toxicity of chemotherapeutics, as well as understanding the drug-drug interactions.

Doppler sonography of the inferior and superior mesenteric arteries in ulcerative colitis.

PURPOSE: The purpose of this study was to evaluate the Doppler sonographic blood-flow parameters and spectral patterns in the inferior mesenteric artery (IMA) and superior mesenteric artery (SMA) in patients with active and inactive (remission-phase) ulcerative colitis (UC). METHODS: The IMAs and SMAs of 25 patients with active-phase UC (group 1), 19 patients with remission-phase UC (group 2), and 22 healthy, asymptomatic subjects (control group) were evaluated by duplex Doppler sonography. The 25 patients in group 1 were categorized into 2 subgroups on the basis of the extent of disease as determined by double-contrast barium enema x-ray study and colonoscopy. The first subgroup (group 1a) consisted of 11 patients with active involvement of the left colon from the rectum to the splenic flexure. The second subgroup (group 1b) consisted of 14 patients with active involvement of the entire colon. The peak systolic velocity (PSV), end-diastolic velocity (EDV), mean velocity (Vmean), resistance index (RI), and pulsatility index (PI) were determined from the Doppler spectral analysis. The inner diameter and cross-sectional area of the IMA and SMA were measured, and the blood-flow volume was calculated. The results were compared between the patient groups and control subjects. RESULTS: In the IMA, the mean blood-flow volume, mean PSV, mean EDV, and Vmean were significantly higher, the mean PI was significantly lower, and the mean diameter and the mean cross-sectional area were significantly larger in group 1 than in group 2 or in the control group (p < 0.001). The mean PSV and the Vmean of the IMA were significantly higher in group 1a than in group 1b (p < 0.05). The mean blood-flow parameters in the SMA were not significantly different between groups 1 and 2 or between either group 1 or group 2 and the control subjects. The mean EDV in the SMA was significantly higher and the mean PI and the mean RI were significantly lower in group 1b than in group 1a (p < 0.01). CONCLUSIONS: Duplex Doppler sonography of the IMA and SMA can be used to evaluate inflammatory disease of the large bowel, to assess disease extent, and to document response to therapy.