Quality of life and impact of pain in women treated with aromatase inhibitors for breast cancer. A multicenter cohort study.

Women with hormone-dependent breast cancer are treated with aromatase inhibitors (AI) to slow disease progression by decreasing estrogen levels. However, AI have adverse effects, including pain, with potentially serious impact on quality of life (QOL) and treatment compliance. We evaluated quality of life during the first year of AI treatment, focusing particularly on the impact of pain. In a multicenter cohort study of 135 women with early-stage breast cancer, free of pain at the initiation of AI treatment, quality of life (by the EORTC QLQ-BR23), somatic and psychic symptoms, psychological characters, temperament and coping strategies were assessed at baseline and at each follow-up visit (1, 3, 6 and 12 months). The impact of treatment-induced pain on quality of life during follow-up was determined with repeated-measures regression models. These models were constructed to assess the effects of pain and pain type on quality of life during follow-up, taking into account predictors associated with quality of life at baseline. Prior ganglion resection, taxane treatment and chemotherapy, a high amplification score on the pain catastrophizing scale, and a high harm avoidance score on the personality questionnaire were associated with a significantly lower baseline QOL. Fifty-seven percent of women developed pain of five different types: upper or lower limb joint pain, diffuse pain, neuropathic pain, tendon pain and mixed pain. A significant decrease in QOL was noted in the women with pain, particularly for body image, sexual functioning and future perspectives. Moreover, the impact of pain on QOL depended on the type of pain experienced. In conclusion, women treated with aromatase inhibitors display changes in quality of life and the degree of change in quality of life depends mostly on the type of pain experienced. Oncologists and patients should be aware of painful adverse effects of AI and encouraged to provide or receive earlier and more appropriate management of these effects.

Sustained response to vemurafenib in a low grade serous ovarian cancer with a BRAF V600E mutation.

Low-grade serous ovarian adenocarcinomas (LGSOC) make up approximately 10 % of serous ovarian carcinomas. While rarely aggressive, this slow-growing tumor is well known to respond poorly to chemotherapy. Specific treatments for this ovarian subtype are lacking, with the same global approaches used for high grade cases being applied for LGSOC patients. LGSOCs have been reported to have a specific genetic profile, with notable implication of the MAPK pathway. This has opened up opportunities for novel therapeutic strategies, with in particular the use of targeted therapies. We report here the case of a heavily pretreated unresectable BRAF p.V600E-mutated LGSOC, which we treated vemurafenib, a BRAF inhibitor specific for V600E mutations. We saw impressive efficacy, with a long-term partial response along with CA125 reductions and symptom relief. Although this mutation is present in LGSOC at very a low incidence, we recommend routine testing for BRAF and other targetable mutations in this patient population, along with further evaluation in the increasingly popular basket trial approach.

Recommendations for bowel obstruction with peritoneal carcinomatosis.

This article reports on the clinical practice guidelines developed by a multidisciplinary group working on the indications and uses of the various available treatment options for relieving intestinal obstruction or its symptoms in patients with peritoneal carcinomatosis. These guidelines are based on a literature review and expert opinion. The recommended strategy involves a clinical and radiological evaluation, of which CT of the abdomen is a crucial component. The results, together with an analysis of the prognostic criteria, are used to determine whether surgery or stenting is the best option. In most patients, however, neither option is feasible, and the main emphasis, therefore, is on the role and administration of various symptomatic medications such as glucocorticoids, antiemetic agents, analgesics, and antisecretory agents (anticholinergic drugs, somatostatin analogues, and proton-pump inhibitors). Nasogastric tube feeding is no longer used routinely and should instead be discussed on a case-by-case basis. Recent studies have confirmed the efficacy of somatostatin analogues in relieving obstruction-related symptoms such as nausea, vomiting, and pain. However, the absence of a marketing license and the high cost of these drugs limit their use as the first-line treatment, except in highly selected patients (early recurrence). When these medications fail to alleviate the symptoms of obstruction, venting gastrostomy should be considered promptly. Rehydration is needed for virtually every patient. Parenteral nutrition and pain management should be adjusted according to the patient needs and guidelines.

Can we predict chemo-induced hematotoxicity in elderly patients treated with pegylated liposomal doxorubicin? Results of a population-based model derived from the DOGMES phase II trial of the GINECO.

INTRODUCTION: Use of anthracyclines is often limited in older patients due to cardiac and hematologic toxicities. Thanks to its reduced toxicity profile, Pegylated Liposomal Doxorubicin (PLD) allows an extended use of doxorubicin to this population. We aimed at modeling PLD-induced hematotoxicity in patients with metastatic breast cancer ≥70 years old and at finding predictive factors of neutrophil nadir value. METHODS: Sixty patients, enrolled in the DOGMES prospective multicentric phase II trial, were treated with PLD at 40mg/m(2) every 28days during six cycles. Trial design included geriatric covariates assessment at inclusion and monitoring of cells count every week for three cycles. A population model was developed to describe hematopoiesis and hematopoietic reserve in these patients. The effect of co-administered G-CSF (granulocyte colony-stimulating factor) was also examined. RESULTS: A pharmacodynamic model was built using data from 53 patients not receiving G-CSF. This model assumed an instantaneous effect of PLD on the system. Based on this model, exact neutrophil nadir value was computed and ranged between 0.069K/mm(3) and 2.63K/mm(3) confirming the weak hematotoxicity of PLD. The same model was then applied to the 7 patients receiving G-CSF and showed that basal neutrophil count was higher for these patients. No other difference was found between both cohorts. Among the covariates collected, three were predictive of neutrophil nadir value: diabetes, frailty syndrome and assistance at home. CONCLUSION: This developed model allowed the identification of predictive factors of nadir ANC and the identification of patients that are more likely to develop hematotoxicity that should be monitored with attention.

A clinical experience of single agent bevacizumab in relapsing ovarian cancer.

OBJECTIVE: The objective of this study is to report the efficacy and tolerance of single agent bevacizumab (BEVA) in relapsing ovarian cancer patients treated in a single institution outside a clinical trial. METHODS: To receive single agent BEVA, patients must have to relapse after at least one previous line of chemotherapy and to not have clinical conditions associated with high risk of gastrointestinal perforation. Dose-intensity of BEVA was 2.5mg/kg/week. RESULTS: 37 previously treated patients (33 with platinum resistant disease) were included in this retrospective analysis. The median number of BEVA infusion by patient was 5 (range: 1-61). The most frequent adverse effect was arterial hypertension, observed in 23 patients (62%), including 11 with G3 (30%) and 1 with G4. No intestinal perforation was reported. Tumor response rate according to CA 125 level (GCIG criteria) was 37% (11 of 30 patients). The median PFS and OS were 4 (range: 1 to +56) and 16 (range: 1 to +65) months (ms), respectively. 12-ms PFS was 25% (95% CI: 11-39%). The PFS tended to be better in patients who experienced grade 3-4 arterial hypertension during the first month of treatment (median: 10ms) compared to patients who did not (median: 3ms) (HR: 0.49 (95% CI: 0.18-1.03), p=0.06 by log rank test). CONCLUSION: Single agent BEVA could be a reasonable option with favorable therapeutic index in pretreated ovarian cancer patients who do not want to suffer the side effects of chemotherapy provided to exclude those with high risk of intestinal perforation and carefully monitor blood pressure.

Symptomatic treatment with lanreotide microparticles in inoperable bowel obstruction resulting from peritoneal carcinomatosis: a randomized, double-blind, placebo-controlled phase III study.

PURPOSE: To investigate the somatostatin analog lanreotide as symptomatic treatment for inoperable bowel obstruction due to peritoneal carcinomatosis. PATIENTS AND METHODS: In all, 80 patients with peritoneal carcinomatosis, inoperable malignant digestive obstruction, and two or more vomiting episodes per day or nasogastric tube (NGT) who were previously treated with intravenous corticosteroids and proton pump inhibitors were randomly assigned to one 30-mg injection of lanreotide microparticles (n = 43) or placebo (n = 37) in a 10-day, double-blind, parallel-group phase. The primary end point was the proportion of patients responding on day 7 (one or fewer episodes of vomiting per day or no vomiting recurrence after NGT removal [for ≥ 3 consecutive days in both cases]). Vomiting frequency/NGT secretion volumes, nausea, abdominal pain, well-being, and safety were also assessed. Patients could then enter an open-label lanreotide-only phase. The study was conducted at 22 European hospitals. RESULTS: More patients receiving lanreotide than placebo were responders; this difference was not statistically significant for the intent-to-treat (ITT) population on the basis of diary cards (primary analysis; 41.9% [18 of 43] v 29.7% [11 of 37], respectively; odds ratio, 1.75; 95% CI, 0.68 to 4.49; P = .24) but was statistically significant for the corresponding supportive per protocol analysis (57.7% [15 of 26] v 30.4% [seven of 23]; P < .05) and ITT analysis, on the basis of investigators' assessments (50.0% [19 of 38] v 28.6% [10 of 35]; P < .05). Improvements in well-being were significantly greater with lanreotide on days 3, 6, and 7. No significant differences were observed for other secondary end points. Only two (mild/moderate) treatment-emergent adverse events were considered related to lanreotide. CONCLUSION: These results show that lanreotide has some efficacy and is safe in the symptomatic treatment of patients with inoperable bowel obstruction due to peritoneal carcinomatosis.