Bevacizumab continuation versus no continuation after first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer: a randomized phase III non-inferiority trial (SAKK 41/06).

BACKGROUND: Chemotherapy plus bevacizumab is a standard option for first-line treatment in metastatic colorectal cancer (mCRC) patients. We assessed whether no continuation is non-inferior to continuation of bevacizumab after completing first-line chemotherapy. PATIENTS AND METHODS: In an open-label, phase III multicentre trial, patients with mCRC without disease progression after 4-6 months of standard first-line chemotherapy plus bevacizumab were randomly assigned to continuing bevacizumab at a standard dose or no treatment. CT scans were done every 6 weeks until disease progression. The primary end point was time to progression (TTP). A non-inferiority limit for hazard ratio (HR) of 0.727 was chosen to detect a difference in TTP of 6 weeks or less, with a one-sided significance level of 10% and a statistical power of 85%. RESULTS: The intention-to-treat population comprised 262 patients: median follow-up was 36.7 months. The median TTP was 4.1 [95% confidence interval (CI) 3.1-5.4] months for bevacizumab continuation versus 2.9 (95% CI 2.8-3.8) months for no continuation; HR 0.74 (95% CI 0.58-0.96). Non-inferiority could not be demonstrated. The median overall survival was 25.4 months for bevacizumab continuation versus 23.8 months (HR 0.83; 95% CI 0.63-1.1; P = 0.2) for no continuation. Severe adverse events were uncommon in the bevacizumab continuation arm. Costs for bevacizumab continuation were estimated to be ∼30,000 USD per patient. CONCLUSIONS: Non-inferiority could not be demonstrated for treatment holidays versus continuing bevacizumab monotheray, after 4-6 months of standard first-line chemotherapy plus bevacizumab. Based on no impact on overall survival and increased treatment costs, bevacizumab as a single agent is of no meaningful therapeutic value. More efficient treatment approaches are needed to maintain control of stabilized disease following induction therapy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, number NCT00544700.

Oxygen delivery and oxygen return in humans exercising in acute normobaric hypoxia.

At a given steady O2 consumption (VO2) in normoxia, cardiac output (Q) is inversely proportional to arterial O2 concentration (CaO2), so that O2 delivery (QaO2=QCaO2) is kept constant and adapted to VO2. The matching between QaO2 and VO2 keeps O2 return (QvO2=QaO2-VO2) constant and independent of VO2 and haemoglobin concentration ([Hb]). This may not be so in hypoxia: in order for QvO2 to be independent of the inspired O2 fractions (FIO2), the slopes of the Q versus VO2 lines should be greater the lower the CaO2, which may not be the case. Thus, we tested the hypothesis of constant QvO2 by determining QaO2 and QvO2 in acute hypoxia. Thirteen subjects performed steady-state submaximal exercise on the cycle ergometer at 30, 60, 90 and 120 W breathing FIO2 of 0.21, 0.16, 0.13, 0.11 and 0.09. VO2 was measured by a metabolic cart, Q by CO2 rebreathing, [Hb] by a photometric technique and arterial O2, saturation (SaO2) by infrared oximetry. CaO2 was calculated from [Hb], SaO2 and the O2 binding coefficient of haemoglobin. The VO2 versus power relation was independent of FIO2. The relations between Q and VO2 were displaced upward and had higher slopes in hypoxia than in normoxia. However, the Q changes did not compensate for those in CaO2. The slopes of the QaO2 versus VO2, lines tended to decrease in hypoxia. QVO2 was lower the lower the FIO2. A significant relationship was found between QvO2 and SaO2 (QvO2= 1.442 SaO2+0.107, r=0.871, n=24, P<10(-7)), which confutes the hypothesis of constant QvO2 in hypoxia.

Mental neuropathy: report of five cases and review of the literature.

Mental nerve neuropathy, also referred to as numb chin syndrome, is a rare, seemingly harmless symptom. It is more often associated with cancer, either as first symptom or during the outcome, than with benign diseases. In this review, we will focus on the numb chin syndrome presenting as an isolated neurological symptom. We report five patients with mental nerve neuropathy associated with metastatic disease (small cell lung cancer, prostatic cancer and breast cancer). In one patient, numb chin syndrome preceded the discovery of the disease, while, in the four others, it occurred as a sign of relapse or progression. Isolated mental nerve neuropathy, frequently associated with breast cancer and lymphoproliferative diseases, is generally thought to be the consequence of bone metastases or leptomeningeal seeding, but may also present without an obvious cause, most often secondary to the involvement of the mental nerve itself. Although various therapies may lead to the resolution of this symptom, median survival after diagnosis is generally less than 1 year. The appearance of a mental nerve neuropathy should never be considered as a 'banal' symptom and investigations to detect a possible cancer should be mandatory.

Sphincter-sparing surgery after preoperative radiotherapy for low rectal cancers: feasibility, oncologic results and quality of life outcomes.

The present study assesses the choice of surgical procedure, oncologic results and quality of life (QOL) outcomes in a retrospective cohort of 53 patients with low-lying rectal cancers (within 6 cm of the anal verge) treated surgically following preoperative radiotherapy (RT, median dose 45Gy) with or without concomitant 5-fluorouracil. QOL was assessed in 23 patients by using two questionnaires developed by the QOL Study Group of the European Organization for Research and Treatment of Cancer: EORTC QLQ-C30 and EORTC QLQ-CR38. After a median interval of 29 days from completion of RT, abdominoperineal resection (APR) was performed in 29 patients (55%), low anterior resection in 23 patients (20 with coloanal anastomosis) and transrectal excision in one patient. The 3-year actuarial overall survival and locoregional control rates were 71.4% and 77.5% respectively, with no differences observed between patients operated by APR or restorative procedures. For all scales of EORTC QLQ-C30 and EORTC QLQ-CR38, no significant differences in median scores were observed between the two surgical groups. Although patients having had APR tended to report a lower body image score (P = 0.12) and more sexual dysfunction in male patients, all APR patients tended to report better physical function, future perspective and global QOL. In conclusion, sphincter-sparing surgery after preoperative RT seems to be feasible, in routine practice, in a significant proportion of low rectal cancers without compromising the oncologic results. However, prospective studies are mandatory to confirm this finding and to clarify the putative QOL advantages of sphincter-conserving approaches.

Infusional ECarboF in patients with advanced breast cancer: a very active and well-tolerated out-patient regimen.

We performed a trial using the combination of epirubicin 50 mg/m2/day 1, carboplatinum AUC 5/day 1 and continuous 5-fluorouracil (5-FU) 200 mg/m2/day (every 4 weeks for 6 months) to confirm the efficacy and low toxicity profile of this regimen in breast cancer. In 51 patients with metastatic (n = 33) or locally advanced (n = 18) breast cancer the overall response rate was 86% (95% confidence interval (95% CI): 73%-94%): 94% in locally advanced and 81% metastatic disease. Grade 3-4 toxicity was low: 4% of patients presented with febrile neutropenia, 16% with severe palmar-plantar syndrome, 10% with Port-a-cath thrombosis. This study confirms the high efficacy of infusional 5-FU-based regimens and justifies further research into novel promising oral 5-FU derivatives.

[Treatment of aggressive non Hodgkin's lymphoma: the experience of a general hospital]. / Traitement des lymphomes non hodgkiniens agressifs: expérience d'un hôpital général.

PURPOSE: The LNH84 regimen for aggressive non Hodgkin's lymphoma consists in an intensive induction phase followed by a consolidation phase. The objectives of this study are to evaluate the feasability and activity of a modified induction phase of this regimen in an oncologic department of a general university hospital. PATIENTS: Twenty-eight consecutive patients receive three or four induction courses of CDBVP corresponding to intravenous cyclophosphamide (C), doxorubicin (D), bleomycin (B), vincristine (V) and oral prednisone (P), for a total of 89 courses. Median age is 42 years and 18 patients are male. IWF is F to J. Fourteen have B symptoms, five a bulky disease, 18 abnormal LDH and nine bone marrow involvement. RESULTS: After the induction phase, 12 patients achieve CR and 11 PR for an overall response rate of 92%. Toxicity consists in severe myelosuppression with a neutropenia WHO grade 4 in all patients. The interval between courses is lengthened for each period, with a median interval of 18.5 days between cycle 1 and 2, 19.5 days between cycle 2 and 3 and 22 days between cycle 3 and 4. Eight patients present an infection WHO grade 3 and one patient died of a treatment related pulmonary complication. At 3 years the overall survival and event free survival is 78% and 57% respectively. CONCLUSIONS: In our experience, the CDBVP protocole is a toxic regimen difficult to administer in a general hospital. Its administration out of a protocole can not be recommanded for good prognosis patients. Its interest for poor prognosis patients should be evaluated with clinical studies.

Uncommon origin for the iliopsoas sign.

The term "iliopsoas sign" has different meanings in the medical literature. Among musculoskeletal disorders, iliopsoas bursitis is probably the most common cause of this clinical sign. Here we report an unexpected vascular pathology in a young man. The only clinical manifestation on examination was an iliopsoas sign.

[Primary Hodgkin disease of the lung]. / Maladie de Hodgkin primaire du poumon.

We describe a patient with a rare primary pulmonary manifestation of Hodgkin's disease who presented with multiple bilateral nodular lesions on the chest x-ray without significant hilar involvement.