Sentinel lymph node biopsy is associated with improved survival compared to level I & II axillary lymph node dissection in node negative breast cancer patients.

OBJECTIVE: The few long-term follow-up data for sentinel lymph node (SLN) negative breast cancer patients demonstrate a 5-year disease-free survival of 96-98%. It remains to be elucidated whether the more accurate SLN staging defines a more selective node negative patient group and whether this is associated with better overall and disease-free survival compared with level I & II axillary lymph node dissection (ALND). METHODS: Three-hundred and fifty-five consecutive node negative patients with early stage breast cancer (pT1 and pT2< or =3 cm, pN0/pN(SN)0) were assessed from our prospective database. Patients underwent either ALND (n=178) in 1990-1997 or SLN biopsy (n=177) in 1998-2004. All SLN were examined by step sectioning, stained with H&E and immunohistochemistry. Lymph nodes from ALND specimens were examined by standard H&E only. Neither immunohistochemistry nor step sections were performed in the analysis of ALND specimen. RESULTS: The median follow-up was 49 months in the SLN and 133 months in the ALND group. Patients in the SLN group had a significantly better disease-free (p=0.008) and overall survival (p=0.034). After adjusting for other prognostic factors in Cox proportional hazard regression analysis, SLN procedure was an independent predictor for improved disease-free (HR: 0.28, 95% CI: 0.10-0.73, p=0.009) and overall survival (HR: 0.34, 95% CI: 0.14-0.84, p=0.019). CONCLUSIONS: This is the first prospective analysis providing evidence that early stage breast cancer patients with a negative SLN have an improved disease-free and overall survival compared with node negative ALND patients. This is most likely due to a more accurate axillary staging in the SLN group.

Prognostic factors affecting long-term outcomes in patients with resected stage IIIA pN2 non-small-cell lung cancer: 5-year follow-up of a phase II study.

The aim was to investigate the efficacy of neoadjuvant docetaxel-cisplatin and identify prognostic factors for outcome in locally advanced stage IIIA (pN2 by mediastinoscopy) non-small-cell lung cancer (NSCLC) patients. In all, 75 patients (from 90 enrolled) underwent tumour resection after three 3-week cycles of docetaxel 85 mg m-2 (day 1) plus cisplatin 40 or 50 mg m-2 (days 1 and 2). Therapy was well tolerated (overall grade 3 toxicity occurred in 48% patients; no grade 4 nonhaematological toxicity was reported), with no observed late toxicities. Median overall survival (OS) and event-free survival (EFS) times were 35 and 15 months, respectively, in the 75 patients who underwent surgery; corresponding figures for all 90 patients enrolled were 28 and 12 months. At 3 years after initiating trial therapy, 27 out of 75 patients (36%) were alive and tumour free. At 5-year follow-up, 60 and 65% of patients had local relapse and distant metastases, respectively. The most common sites of distant metastases were the lung (24%) and brain (17%). Factors associated with OS, EFS and risk of local relapse and distant metastases were complete tumour resection and chemotherapy activity (clinical response, pathologic response, mediastinal downstaging). Neoadjuvant docetaxel-cisplatin was effective and tolerable in stage IIIA pN2 NSCLC, with chemotherapy contributing significantly to outcomes.

Fatigue and menopausal symptoms in women with breast cancer undergoing hormonal cancer treatment.

BACKGROUND: Hormonal treatment for women with breast cancer is frequently proposed in the adjuvant as well as in the palliative setting. Therefore, many women are confronted with early menopause and prolonged oestrogen deprivation and consequently with a variety of quality of life issues, such as menopausal symptoms and fatigue. PATIENTS AND METHODS: It was the aim of this study to explore the occurrence and frequency of menopausal symptoms in women with breast cancer, undergoing hormonal cancer treatment and to investigate their relationship with fatigue. A cross-sectional, quantitative approach was used in this multi-centre study. The Checklist for Patients with Endocrine Therapy (C-PET) and the International Breast Cancer Study Group (IBCSG) Linear Analogue Scales for patients with endocrine treatment were used. Descriptive statistics, as well as cluster analyses were performed. RESULTS: Most frequent menopausal symptoms involved hot flashes/sweats, tiredness, weight gain, vaginal dryness and decreased sexual interest. There were significant differences between the fatigued and the non-fatigued population regarding the intensity of menopausal symptoms, emotional irritability and general coping. Cluster analyses supported a menopausal symptom cluster. CONCLUSIONS: Fatigue accompanies menopausal symptoms and an association can be expected. Methods for routine screening for menopausal symptoms, including fatigue, are suggested as a relevant research issue in women with breast cancer undergoing hormonal treatment.

Vinorelbine in androgen-independent metastatic prostatic carcinoma--a phase II study.

The purpose of this study was to evaluate the efficacy of vinorelbine treatment in terms of prostate-specific antigen (PSA) response and clinical benefit (decrease of pain or analgesic score for the subgroup of patients with pain), as well as its toxicity in patients with progressive metastatic androgen-independent prostatic carcinoma. 44 patients with prostatic carcinoma progressing after orchiectomy or during treatment with hormonal agents were treated with vinorelbine at a dose of 30 mg/m(2) intravenously (i.v.) on days 1 and 8 of a 21-day cycle. Inclusion criteria were metastatic progressive prostatic carcinoma with prostate-specific antigen (PSA) serum levels >/=3 x upper limit of normal, World Health Organization (WHO) performance status /=2 was observed on the day of scheduled vinorelbine administration. 9 patients received less than three cycles, 6 due to rapid tumour progression. Treatment at day 1 had to be delayed in 13.7% of 183 cycles. Treatment at day 8 had to be omitted in 19.7% of all cycles. Grade >/=3 granulocytopenia occurred in 18% of patients. 4 patients had severe constipation. In 7 patients (15.9%, Confidence Interval (CI) 6.6-30.1%), a PSA response (>/=50% reduction of PSA levels) was observed. Among 8 patients with measurable disease, 3 had partial remission and 1 no change. Median time to PSA progression in 43 assessable patients was 11.9 weeks (range 3-52 weeks). Median duration of PSA response was 14 weeks (9-30 weeks). Clinical benefit was seen in 7 of 31 cases (23%) with baseline pain, there was no association with PSA response. Vinorelbine is a fairly well tolerated drug with a moderate single agent activity in patients with androgen-refractory prostate cancer.

Randomized controlled trial of laparoscopic transabdominal preperitoneal hernioplasty vs Shouldice repair.

BACKGROUND: There is a scarcity of data on long-term results after laparoscopic hernia repair. Herein we report on the outcome of a group of patients who were followed up for 5 years in a multicenter study on hernia repair. METHODS: A total of 100 patients with 127 hernias were randomized to undergo either transabdominal preperitoneal (TAPP) or Shouldice hernia repair. Follow-up was by clinical examination and standardized questionnaire. RESULTS: Of the 100 patients who underwent surgery, 84 were available for follow-up at 5 years. The TAPP procedure was less painful than the Shouldice repair, with fewer patients receiving narcotic analgesics. The median time to return to 100% activity was shorter in the laparoscopic group (21 days) than in the Shouldice group (40 days). Up to 60 months after the operation, the complication rate was lower in laparoscopically repaired hernias (19/66) than in the open group (25/61). There were two recurrences (3.9%) in the TAPP group and five in the Shouldice group (10.2%). CONCLUSION: The TAPP hernia repair yields comparable or better results than Shouldice herniorrhaphy in terms of postoperative pain, recovery, and recurrence rate.

Reduced dose of subcutaneous cladribine induces identical response rates but decreased toxicity in pretreated chronic lymphocytic leukaemia. Swiss Group for Clinical Cancer Research (SAKK).

PURPOSE: To study the efficacy and the safety of cladribine (2-chlorodeoxyadenosine, 2-CDA) administered as 24-hour infusions or as subcutaneous bolus injections at two different doses to patients with relapsing or refractory chronic lymphocytic leukaemia (CLL). PATIENTS AND METHODS: In this non randomised 2-cohort study, 20 patients with pretreated CLL received cladribine at a dose of 0.7 mg/kg/cycle as continuous i.v. infusions over seven days (group 1) and 35 patients were treated at a reduced dose of 0.5 mg/kg/cycle given as s.c. bolus injections for five days (group 2). After two cycles of four week duration, response was assessed. In the case of progressive disease, therapy was discontinued, otherwise a maximum of four additional cycles were administered until best response. RESULTS: A total of 130 cycles were administered (group 1: 41, group 2: 89). Patient characteristics in both groups were comparable. The median dose intensities were 0.172 mg/kg per week and 0.123 mg/kg per week for groups 1 and 2, respectively (P < or = 0.0001). The overall response rate for all 55 patients was 38% (95% confidence interval (95% CI): 25%-52%), with 5% CR and 33% PR. Response was similar in both patient groups (35% in group 1, 40% in group 2). No association between cladribine dose intensity and response rate was found, and there was no difference between patients relapsing after or refractory to previous therapies (11 of 24 vs. 10 of 31). Median remission duration was six months in both groups. Toxicity, in particular infections (all WHO grades, 34% in group 1 versus 7% in group 2) and myelosuppression (grade 1-4 neutropenia, 72% versus 41% of cladribine cycles) were statistically significantly more frequent in group 1. CONCLUSION: Cladribine is active in heavily pretreated patients with chronic lymphocytic leukaemias. Dose reduction by 29% led to similar response and remission duration, but to a significant decrease of myelotoxicity and risk of infection. Cladribine administered as s.c. bolus injections at 0.5 mg/kg per cycle is safe and this dose level should not be exceeded in this patient population.

Cladribine (2-CDA) given as subcutaneous bolus injections is active in pretreated Waldenström's macroglobulinaemia. Swiss Group for Clinical Cancer Research (SAKK).

Clinical trials with intravenous cladribine infusions in pretreated patients with Waldenström's macroglobulinaemia have shown a response rate of 40%. Our pharmacokinetic studies revealed that the bioavailability of subcutaneous cladribine is complete but that the concentration-time profile is very different from intravenous administration. We designed this phase II multi-institutional trial to study the activity and toxicity of cladribine given as s.c. bolus injections in patients with symptomatic Waldenström's macroglobulinaemia. Between May 1993 and October 1995, 25 patients were accrued: male/female 18/7, median age 65 years (range 44-85). All except one patient had been pretreated with more than one regimen (median 2, range 0-10). 18 patients had progressed under previous therapy and six were in relapse. All patients received cladribine for a total dose of 0.5 mg/kg per cycle as s.c. bolus injections divided over 5 d at > or = 4 week intervals, for a maximum of six cycles. All 25 patients were evaluable for toxicity and response. A total of 67 cycles were administered (median 3 cycles, range 1-6). Overall response rate including disease stabilization which had been progressive under previous therapy was 68%. 10 patients (40%, 95% CI 21-61%) achieved a partial remission. Seven responders had been progressive under previous therapy. Maximum responses were reached no later than the third cycle. Median time to treatment failure and remission duration were 4.4 (range 0.5-33) and 8 months (5-29), respectively. Four patients (16%) suffered from infections W.H.O. grade > or = 2 (pneumonia grade 2, Staphylococcus septicaemia grade 3, viral encephalitis and pneumonia, both grade 4 with complete resolution). No other severe adverse events were observed. Cladribine given as s.c. 5 d bolus injections was found to be active in pretreated Waldenström's macroglobulinaemia and resulted in durable remissions.

Formestane versus megestrol acetate in postmenopausal breast cancer patients after failure of tamoxifen: a phase III prospective randomised cross over trial of second-line hormonal treatment (SAKK 20/90). Swiss Group for Clinical Cancer Research (SAKK)

The aim of the study was to compare efficacy and tolerability of the new aromatase inhibitor formestane (Lentaron) with megestrol acetate (Megestat) (MGA) in postmenopausal patients with advanced breast cancer. 179 patients were randomised to receive either 250 mg formestane intramuscularly biweekly or MGA 160 mg orally daily. 51% of the patients had received tamoxifen as adjuvant treatment; 73% of the patients had positive and 16% unknown oestrogen receptor values. The response rate was 17% in both treatment arms (95% confidence interval 10-26% for formestane and 10-27% for MGA). Disease stabilisation > or = 6 months was seen in 25% of the formestane and 22% of the MGA patients. Time to treatment failure was 120 days in the formestane arm and 111 days in the MGA arm. There was no significant difference between the treatments with regard to response rate and time to treatment failure. Overall toxicity was similar in both arms, but weight gain > 3 kg (P = 0.081) and severe cardiovascular toxicity (P = 0.044) were more frequently observed with MGA, e.g. deep vein thrombosis 0/90 formestane versus 5/81 MGA cases (P = 0.022). Formestane was associated with worsening of hot flushes/sleeping problems (P = 0.051) and mild leucopenia (P = 0.004). In our study, formestane and MGA showed similar antineoplastic activity as second-line hormonal treatment for advanced breast cancer. Both drugs have a specific toxicity profile. MGA was associated with significantly more severe cardiovascular toxicity and weight increase than formestane.