Adjuvant extension of chemotherapy after neoadjuvant therapy may not improve outcome in early-stage breast cancer

Introduction

Neoadjuvant chemotherapy (NAC) is equivalent to adjuvant therapy (AdC) in terms of survival and disease-free interval. Many institutions add AdC after NAC and surgery. However, such extended chemotherapy (ExC) is not evidence based. Study aim was to investigate if ExC improved disease-free (DFS) and overall survival (OS).

Patients and Methods

From 1998 to 2006 356 consecutive patients received NAC (45 pts), AdC (221 pts) or ExC (90 pts). We analysed these 3 groups to determine effects of ExC and to identify patients who might benefit. NAC consisted in 93% of 3–6 cycles of epirubicin + docetaxel, AdC comprised EC ± taxanes in 72%. Median age in the NAC, AdC, and ExC-groups was 54, 56 and 52 years with follow-up of 30, 57, and 55 months.

Results

After NAC, 35% achieved downstaging and 10% pathologic complete remission. Surprisingly ExC seemed to result in reduction of 5-year DFS: compared to 85% and 82% after NAC and AdC, DFS was 61% after ExC (p = 0.001). OS was not significantly affected (79, 91, and 78% after NAC, AdC and ExC, p = 0.13). In multivariate analysis after correction for age, menopausal status, stage, grading, hormone receptors, her2-status, radiotherapy and surgery, ExC seemed to adversely affect DFS (HR 2.15, p = 0.008), loco-regional and distant recurrence-rates (HR 3.0, p = 0.03 and HR 2.0, p = 0.02).

Discussion

In this single-center analysis ExC could not show advantages in terms of DFS and OS. Because multivariate analyses of retrospective data cannot account for all potential biases, these data require confirmation in randomized clinical trials. Until then, extended chemotherapy should be considered carefully. As in previous studies, no differences were found between NAC and AdC groups.     

Unsuspected Primary Tubal Carcinoma during Operative Laparoscopy

Objective.To evaluate the possible risk of dealing with an unsuspected primary carcinoma of the fallopian tube during laparoscopic surgery.Methods.We performed a countrywide survey in Austria concerning laparoscopic procedures in cases of primary carcinoma of the tube. The questionnaire consisted of questions regarding the pre-, intra-, and postoperative management.Results.Of 18,435 laparoscopies in cases of an adnexal mass, 5 cases were reported, when laparoscopy was performed on an unsuspected carcinoma of the tube. Therefore, the risk of detecting this malignancy during laparoscopy after preoperative evaluation is 1 in 3687 cases (0.028%).Conclusion.The risk of encountering an unsuspected primary carcinoma of the fallopian tube during laparoscopy in Austria is an extremely rare situation. In case of a malignancy, a staging or debulking laparotomy should be performed immediately or as soon as possible.     

Kala-azar acquired in Croatia]

Six weeks after his return from a two-week vacation in Croatia a 52 year-old janitor from Graz complained of loss of appetite, fever, headache, and a 9-kg weight loss. The spleen was enlarged to 16cm as measured by sonography. Laboratory tests revealed pancytopenia, a prolonged prothrombin time and elevation of serum LDH concentration. While repeated bone marrow biopsy showed no signs of leishmaniasis, high antibody titers against leishmania antigen led to the diagnosis of kala-azar. The indirect immunofluorescent antibody test (1:128) and a haemagglutination-inhibition test (1:512) showed diagnostic elevations of titers. Therapy with pentostam led to prompt defervescence and resulted in a full recovery of the patient. After six weeks a marked decrease of antibody titers in the haemagglutination-inhibition test (1:16) could be observed. Leishmaniasis has to be considered in patients with fever of unknown origin who return from Mediterranean countries. Despite a negative bone marrow biopsy a diagnosis is possible on the basis of serological tests. This is important because effective therapy is available as illustrated by this patient and because of the fact that the disease runs a lethal course if the diagnosis is missed.     

Efficacy and safety of rizatriptan wafer for the acute treatment of migraine

Rizatriptan is a potent, highly selective 5HT1B/1D agonist with rapid onset of action for acute treatment of migraine. Rizatriptan wafer is a novel, freeze-dried dosage formulation of rizatriptan which rapidly disintegrates on the tongue, is swallowed with saliva, and may be taken without liquids. The efficacy and tolerability of rizatriptan wafer were examined in a placebo-controlled, double-blind, outpatient study in 555 migraineurs. The primary efficacy endpoint was pain relief at 2 h. From 30 min onwards, significantly more patients experienced pain relief and became pain-free after rizatriptan 10-mg wafer compared to placebo. At 2 h, the percentage of patients with pain relief was significantly higher after rizatriptan 10-mg wafer (74%), 5-mg wafer (59%) compared with placebo (28%). Rizatriptan 10-mg wafer was superior to rizatriptan 5-mg wafer on pain relief at 1.5 and 2 h (p < 0.05). Significantly more patients were pain-free at 2 h after rizatriptan 10-mg wafer (42%), 5-mg wafer (35%) compared with placebo (10%). Both doses of rizatriptan wafer were well tolerated. Rizatriptan wafer is a convenient, highly effective new formulation for acute treatment of migraine.     

Randomized study of didanosine monotherapy and combination therapy with zidovudine in hemophilic and nonhemophilic subjects with asymptomatic human immunodeficiency virus-1 infection. AIDS Clinical Trial Groups

To evaluate the safety and efficacy of didanosine (ddl) monotherapy and three different combinations of zidovudine (ZDV) and ddl in asymptomatic human immunodeficiency virus-1 (HIV-1) infection, we conducted an open-label, phase I/II study in 126 asymptomatic HIV-1- infected hemophilic and nonhemophilic subjects with a CD4 count of 200 to 500/mm3 stratified for prior zidovudine treatment and baseline CD4 count. Study arms included arm A, low-dose combination (ZDV 150 mg and ddl 134 mg, daily); arm B, moderate-dose combination (ZDV 300 mg and ddI 334 mg, daily); arm C, high-dose combination (ZDV 600 mg and ddl 500 mg, daily), and arm D, ddl monotherapy (ddl 500 mg, daily). Earlier, more frequent hepatotoxicity was experienced by hemophilic subjects (P = .008), but there were no differences in toxicity between treatment arms (P = .51), nor were there any differences in the rate of development of clinical endpoints by treatment (P = .41). Smaller median CD4 increases occurred over the first 12 weeks for arms A and D, 44/mm3 and 42/mm3, than arms B and C, 105/mm3 and 114/mm3, respectively, (P = .015). Hemophilia status (P = .0004) and prior ZDV experience (P = .044) independently predicted weaker CD4 responses during the first 12 weeks of treatment. Using a regression model and adjusting for hemophilia status, prior ZDV treatment, and baseline CD4, there was a significant reduction in quantitative viral load from baseline by week 12 for all treatment arms combined (P = .0001), with significantly lower median percent reduction for arm A (56.3%) than arms B, C, and D (94.6%, 98.5%, and 91.9%, respectively, P = .015). Although greater hepatoxicity and weaker CD4 responses occur in hemophilic subjects, didanosine monotherapy and combination therapy with zidovudine are safe and effective in asymptomatic HIV-1-infected patients.