Pain and fertility outcomes of nerve-sparing, full-thickness disk or segmental bowel resection for deep infiltrating endometriosis-A prospective cohort study.

INTODUCTION: Choosing the optimal treatment for bowel endometriosis, ie, conservative vs radical surgery, is under debate. We aimed to evaluate the surgical outcomes of segmental resection and disk resection regarding fertility, pain symptoms, and quality of life score of women with colorectal deep infiltrating endometriosis. MATERIAL AND METHODS: From March 2011 to December 2016, 134 consecutive patients with symptomatic deep infiltrating endometriosis of the rectosigmoid up to 25 cm from the anal verge undergoing segmental resection or disk resection were prospectively evaluated regarding reduction in pain symptoms, fertility outcomes, and complication rates according to Clavien-Dindo classification. RESULTS: Of the 134 women included, segmental resection was performed in 102 (76.1%) women and disk resection was performed in 32 (23.9%) women. There was no difference in duration of surgery, complication rates, mean hospital stay, or discrepancy in hemoglobin level comparing the two groups. There was no significant difference regarding reduction of pain symptoms, fertility, and functional outcomes. One hundred and twelve (83.6%) women were followed up long-term. In both cohorts, there was a significant reported decrease in pain symptoms and increase in quality of life scores. Of all the 61 infertile women, 26 (42.6%) became pregnant spontaneously, and 13 (21.3%) by in vitro fertilization with an overall pregnancy rate of 63.4%. The overall complication rate (Clavien-Dindo III-IV) was 8 of 134 (5.9%) without statistically significant difference between the cohorts. CONCLUSIONS: Both conservative surgery with disk resection, and nerve- and vessel-sparing segmental resection reduce pain symptoms with equal morbidity. Fertility is improved with surgery with both techniques.

Treatment of recurrent platinum-resistant ovarian cancer with pegylated liposomal doxorubicin--an evaluation of the therapeutic index with special emphasis on cardiac toxicity.

BACKGROUND: To study the efficacy of pegylated liposomal doxorubicin (PLD) at a modified dose of 45 mg/m(2) every 4 weeks in platinum-resistant ovarian cancer and to evaluate toxicities and effects on quality of life (QoL) of this single-agent regimen. METHODS: Treatment response was evaluated by CT scan or CA 125 levels. Toxicity and QoL was recorded according to the common toxicity criteria of the National Cancer Institute and the EORTC QLQ-C30 questionnaire, respectively. RESULTS: Eighty-five patients entered this nationwide observational study (384 cycles administered) and 4 (4.7%) achieved complete and 22 (25.8%) partial remission, giving an objective response rate of 30.5%. Eight patients experienced therapy-limiting side effects prompting discontinuation of treatment. Palmoplantar erythrodysesthesia (PPE) and/or stomatitis were the main reasons for discontinuation. Grade 3-4 PPE and stomatitis occurred in 4.2 and 2.2% of the 384 cycles, respectively. Grade 3-4 cardiotoxicity was absent and overall QoL was not significantly decreased following PLD treatment. CONCLUSION: Single-agent PLD at a dose of 45 mg/m(2) is an efficient treatment in recurrent platinum-resistant ovarian cancer and exhibits an exceptionally favorable therapeutic index.

Analysis of trastuzumab and chemotherapy in advanced breast cancer after the failure of at least one earlier combination: an observational study.

BACKGROUND: Combining trastuzumab and chemotherapy is standard in her2/neu overexpressing advanced breast cancer. It is not established however, whether trastuzumab treatment should continue after the failure of one earlier combination. In this trial, we report our experience with continued treatment beyond disease progression. METHODS: Fifty-four patients, median age 46 years, range 25-73 years, were included. We analysed for time to tumour progression (TTP) for first, second and beyond second line treatment, response rates and overall survival. RESULTS: Median time of observation was 24 months, range 7-51. Response rates for first line treatment were 7.4% complete remission (CR), 35.2% partial remissions (PR), 42.6% stable disease > 6 months (SD) and 14.8% of patients experienced disease progression despite treatment (PD). Corresponding numbers for second line were 3.7% CR, 22.2% PR, 42.6% SD and 31.5% PD; numbers for treatment beyond second line (60 therapies, 33 pts 3rd line, 18 pts 4th line, 6 pts 5th line, 2 pts 6th line and 1 patient 7th line) were 1.7% CR, 28.3% PR, 28.3% SD and 41.6% PD respectively. Median TTP was 6 months (m) in the first line setting, and also 6 m for second line and beyond second line. An asymptomatic drop of left ventricular ejection fraction below 50% was observed in one patient. No case of symptomatic congestive heart failure was observed. CONCLUSION: The data presented clearly strengthen evidence that patients do profit from continued trastuzumab treatment. The fact that TTP did not decrease significantly from first line to beyond second line treatment is especially noteworthy. Still, randomized trials are warranted.

Prognostic value of monitoring tumour markers CA 15-3 and CEA during fulvestrant treatment.

BACKGROUND: At many centres tumour markers are used to detect disease recurrence and to monitor response to therapy in patients with advanced disease, although the real value of serial observation of marker levels remains disputed. In this study, we evaluated the prognostic value of tumour markers for predicting response (partial response [PR], stable disease [SD] > or = 6 months), de novo disease progression (PD) and secondary PD in patients receiving fulvestrant ('Faslodex') 250 mg/month for the treatment of metastatic breast cancer (MBC). METHODS: Changes in cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) were prospectively monitored (monthly) and were also evaluated for the 3 months preceding secondary PD. Data from 67 patients with previously treated MBC participating in a Compassionate Use Programme were analysed. RESULTS: In patients with a PR (n = 7 [10.4%]), a non-significant increase in CA 15-3 occurred during the first 6 months of treatment; CEA was significantly reduced (P = 0.0165). In patients with SD >/= 6 months (n = 28 [41.8%]), both CA 15-3 (P < 0.0001) and CEA (P = 0.0399) levels increased significantly after 6 months treatment. In those experiencing de novo PD (n = 32 [47.8%]), CA 15-3 increased significantly (P < 0.0001) after 4 months; CEA also increased significantly (P = 0.0002) during the same time period. Both CA 15-3 (P < 0.0001) and CEA (P < 0.0001) increased significantly in the 3 months preceding secondary PD. CONCLUSION: CA 15-3 increases in patients progressing on fulvestrant but may also increase in those experiencing clinical benefit; this should not be taken as a sign of PD without verification. Overall, both CA 15-3 and CEA appear to be poor prognostic markers for determining progression in patients receiving fulvestrant.

Oral vinorelbine alone or in combination with trastuzumab in advanced breast cancer: results from a pilot trial.

INTRODUCTION: We evaluated the efficacy of oral vinorelbine (OV) (Navelbine oral Boeringer-Ingelheim Austria) in patients with advanced breast cancer as first-line therapy or after progressing under earlier line chemotherapies alone or in combination with trastuzumab (T). PATIENTS AND METHODS: Seventy-eight patients [median age: 63.5 years (y), range (r): 38-84 years] were included into this trial. Patients with her-2/neu positive tumours received a combination of OV and T. Treatment effect was evaluated every three cycles and treatment continued until progression. OV was administered in a dose of 60 mg/m(2) on day 1 and 8, q = 21 days, and no dose escalation to 80 mg/m(2) was performed. RESULTS: We observed a complete response in 5.9% of patients, partial remission in 22.1%, stable disease (SD) > 6 months in 33.8%, SD < 6 months in 2.9%, and progression despite treatment in 35.3%, respectively. Time to progression was 6 months (range 1-23+). The main toxicities consisted of nausea/vomiting (N/V) and neutropenia. Grade IV neutropenia was found in 5 patients (6.4%), grade III in 6 patients (7.7%) and grade I and II in 11.5%. We did not find any grade IV N/V in our patients, however, grade III N/V was observed in 3.8%. No other grade III and IV toxicities were reported. CONCLUSION: OV appears to be effective in the treatment of advanced breast cancer at the dose and schedule chosen. It is well tolerated, effective, and the oral formulation is an advantage for the patients as well as for the nursing staff.

Minimal stimulation using recombinant follicle-stimulating hormone and a gonadotropin-releasing hormone antagonist in women of advanced age.

OBJECTIVE: To determine whether minimal stimulation with short-term application of low-dose recombinant follicle-stimulating hormone (FSH) together with a gonadotropin-releasing hormone (GnRH) antagonist represents a cost-effective treatment regimen for patients with elevated FSH levels, aged 40 and above. DESIGN: Retrospective cohort study. SETTING: Academically affiliated private in vitro fertilization (IVF) program. PATIENT(S): Eighty-five IVF cycles using minimal ovarian stimulation and 85 cycles with a standard long-stimulation protocol, conducted between January 2000 and January 2002, in women aged 40 and above who had slightly increased FSH levels. INTERVENTION(S): Patients on the long protocol underwent standard cycle monitoring and stimulation. In contrast, women with minimal stimulation had transvaginal sonography initiated on day 8 of the menstrual cycle and at a follicle size of 13 mm. We administered 0.25 mg of GnRH antagonist and 75 IU recombinant FSH daily until ovulation induction. MAIN OUTCOME MEASURE(S): Numbers of oocytes, and rates of cancellation and pregnancy. RESULT(S): Minimal stimulation cycles resulted in a clinical pregnancy rate of 8.2% per started cycle and 10% per embryo transfer (ET), whereas the control group yielded a clinical pregnancy rate of 10.6% per started cycle and of 10.7% per ET (not statistically significant). CONCLUSION(S): In women aged 40 and above with abnormal FSH levels, minimal stimulation protocol achieves similar pregnancy rates to a standard protocol, and thus represents a cost-effective alternative.

Preoperative chemotherapy with epidoxorubicin, docetaxel and capecitabine plus pegfilgrastim in patients with primary breast cancer.

The objective of this pilot trial was to evaluate the safety and activity profile of epidoxorubicin, docetaxel and oral capecitabine plus pegfilgrastim (TEX+P) as preoperative first-line treatment for patients with breast cancer. Eleven consecutive patients were enrolled in this prospective clinical pilot trial. Preoperative treatment consisted of epidoxorubicin [75 mg/m2 body surface area (BSA)] and docetaxel (75 mg/m2 BSA) administered sequentially on day 1 in combination with oral capecitabine 2000 mg/m2 daily divided into two doses on days 1-14 of each 3-week treatment cycle. Pegfilgrastim 6 mg fixed dose was administered s.c. on day 2 of every treatment cycle. Patients received a total of 58 cycles (median 6 cycles, range 1-6) of this therapeutic regimen. Outpatient TEX+P was well tolerated. No WHO grade IV toxicity was observed. A pathological major response to this preoperative therapy regimen could be demonstrated in eight of nine evaluable patients leading to breast-conserving surgery in seven of nine evaluable patients. We conclude that outpatient TEX+P is safe in the neoadjuvant treatment of patients with primary breast cancer. Thus, this regimen can be considered for further clinical trials.

Darbepoetin alpha as treatment for anemia in patients receiving chemotherapy: a single-center experience.

We evaluated Darbepoetin alpha (Aranesp; Amgen), a novel erythropoietic protein, in patients who developed anemia while receiving chemotherapy. Seventy-five patients (median age 62 years, range 40-81 years) undergoing different cancer chemotherapy regimens were treated with darbepoetin alpha. Therapy was started if hemoglobin (Hb) levels fell below 10 g/dl or if symptomatic anemia developed. Treatment effect was evaluated after 4 weeks, 8 weeks and at the end of therapy (up to 12 weeks). If no increase in Hb was seen after 4 weeks, the dose of darbepoetin alpha was increased to 300 microg. Patients were questioned about fatigue and any change during treatment, with evaluation according to a four-point scale, where 0 = no fatigue and 3 = severe fatigue. We observed a treatment response in 54 of 75 patients (72%). Dose escalation was necessary in 30 of 75 patients (40%) and blood transfusions were required in 13 of 75 patients (17.3%). Response was observed in 32 of 43 patients (74.4%) who had a baseline Hb < 10 g/dl and in 22 of 32 (68.8%) patients who had a baseline Hb > or =10 g/dl. At baseline, 60 of 75 patients (93.3%) reported fatigue of grade 2 or 3, but at the end of the 12-week follow-up period, only 26 of 68 patients (38.3%) reported fatigue at these levels. We conclude that darbepoetin alpha is a highly effective and well-tolerated drug in the treatment of chemotherapy-associated anemia. Patients benefited both in terms of Hb levels and control of chemotherapy-related symptoms.

Zoledronate in a patient with pamidronate refractory hypercalcemia syndrome.

Hypercalcemia of malignancy remains a common metabolic complication of advanced cancer often resulting in considerable morbidity and diminishing life quality in the later stages of disease. Bisphosphonates, especially zoledronic acid, are potent inhibitors of bone resorption and are the most effective therapy for hypercalcemia of malignancy. We report on the course of disease in a 51-year-old woman who presented with metastatic breast cancer that had relapsed to the liver. The patient suffered from a pamidronate-refractory paraneoplastic hypercalcemia, which caused a confused mental status and compromised her already severely limited life quality. Only with the introduction of zoledronate could the patient's hypercalcemia be normalized with consecutive regain of an acceptable life quality.