Evaluation of tamoxifen and anastrozole in the prevention of gynecomastia and breast pain induced by bicalutamide monotherapy of prostate cancer.

PURPOSE: To determine whether tamoxifen or anastrozole prevents gynecomastia and breast pain caused by bicalutamide (150 mg) without compromising efficacy, safety, or sexual functioning. PATIENTS AND METHODS: A double-blind, placebo-controlled trial was performed in patients with localized, locally advanced, or biochemically recurrent prostate cancer. Patients (N = 114) were randomly assigned to either bicalutamide (150 mg/d) plus placebo or in combination with tamoxifen (20 mg/d) or anastrozole (1 mg/d) for 48 weeks. Gynecomastia, breast pain, prostate-specific antigen (PSA), sexual functioning, and serum levels of hormones were assessed. RESULTS: Gynecomastia developed in 73% of patients in the bicalutamide group, 10% of patients in the bicalutamide-tamoxifen group, and 51% of patients in the bicalutamide-anastrozole group (P < .001); breast pain developed in 39%, 6%, and 27% of patients, respectively (P = .006). Baseline PSA level decreased by > or = 50% in 97%, 97%, and 83% of patients in the bicalutamide, bicalutamide-tamoxifen, and bicalutamide-anastrozole groups, respectively (P = .07); and adverse events were reported in 37%, 35%, and 69% of patients, respectively (P = .004). There were no major differences among treatments in sexual functioning parameters from baseline to month 6. Elevated testosterone levels occurred in each group; however, free testosterone levels remained unchanged in the bicalutamide-tamoxifen group because of increased sex hormone-binding globulin levels. CONCLUSION: Anastrozole did not significantly reduce the incidence of bicalutamide-induced gynecomastia and breast pain. In contrast, tamoxifen was effective, without increasing adverse events, at least in the short-term follow-up. These data support the need for a larger study to determine any effect on mortality.     

Upfront high-dose sequential therapy (HDS) versus VACOP-B with or without HDS in aggressive non-Hodgkin's lymphoma: long-term results by the NHLCSG.

BACKGROUND: There is not univocal concordance for using high-dose sequential therapy (HDS) as first-line treatment for aggressive non-Hodgkin's lymphoma (NHL). We designed this study to evaluate the usefulness of HDS followed by high-dose therapy (HDT) with autologous stem cell transplantation as front-line treatment in different subsets of aggressive NHL. PATIENTS AND METHODS: Among 223 patients aged 15-60 years with aggressive, advanced stage NHL, 106 patients were randomized to VACOP-B (etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin) for 12 weeks (plus HDS/HDT in case of persistent disease) (arm A), and 117 patients to VACOP-B for 8 weeks plus upfront HDS/HDT (arm B). RESULTS: According to the intention-to-treat analysis, the complete response rate was 75% for arm A and 72.6% for arm B. With a median follow-up of 62 months there was no difference in 7-year probability of survival (60% and 57.8%; P = 0.5), disease-free survival (DFS) (62% and 71%; P = 0.2) and progression-free survival (PFS) (44.9% and 40.9%; P = 0.7) between the two arms. Subgroup analyses confirmed that the best results in terms of survival, DFS and PFS were achieved by patients with large B-cell NHL without bone marrow (BM) involvement, independently of the treatment arm. Results were poorer in other categories of patients and poorest in patients with BM involvement. CONCLUSIONS: Aggressive NHL patients do not benefit from upfront HDS/HDT.     

Switching to anastrozole versus continued tamoxifen treatment of early breast cancer: Long term results of the Italian Tamoxifen Anastrozole trial

The Italian Tamoxifen Anastrozole (ITA) trial investigated the efficacy of switching to anastrozole for women who were already on adjuvant tamoxifen since 2–3 years. Relapse-free survival (RFS) was the primary end-point; event-free survival (EFS), overall survival (OS) and safety were secondary end-points. Herein, we report an update on the long term results of this trial.At a median follow-up time of 128 months (range14–168 months), 94 events have been recorded in the tamoxifen group compared with 71 events in the anastrozole group (hazard ratio (HR) = 0.71; 95% confidence interval (CI), 0.52–0.97; p = 0.03). RFS was also significantly longer in the anastrozole group (HR = 0.64; 95% CI, 0.44–0.94; p = 0.023); no statistically significant difference between study arms concerning OS was shown, but the trial was not powered enough in respect to this end-point. The incidence of serious adverse events (SAE) like bone fractures was comparable (four in each arm), while gynaecological problems were still significantly more numerous among the women continued on tamoxifen (21 patients developed a SAE in this group, including eight endometrial cancers, compared to three patients who suffered from a SAE, including one endometrial cancer, in the anastrozole group: p < 0.000).Present data confirm that switch is safe and can provide long-term gain in terms both of RFS and of EFS, which persists even several years since treatment discontinuation.     

Chemotherapy with or without estrogenic recruitment in metastatic breast cancer. A randomized trial of the Gruppo Oncologico Nord Ovest (GONO)

BACKGROUND:: This phase III study was carried out to verify whether a kineticrecruitment induced with low doses of diethylstilbestrol (DES)could increase the antitumor activity of chemotherapy in patientswith advanced breast cancer. PATIENTS AND METHODS:: Two hundred fifty-eight women with metastatic breast cancerwere randomized to receive chemotherapy consisting of cyclophosphamide600 mg/sqm i.v., epidoxorubicin 60 mg/sqm i.v. and fluorouracil600 mg/sqm i.v. (CEF) on day 1 or DES-CEF (diethylstilbestrol1 mg orally days 1–3 CEF on day 4) every 21 days. Patientswere treated until progression or, if responsive, for a maximumof 10 courses. RESULTS:: There were no significant differences between the two treatmentarms in response rates (51.3% to CEF and 49.6% for DES-CEF);median progression-free survival (9.4 months for CEF and 11months for DES-CEF group) or median overall survival (17.3 and20 months for CEF and DES-CEF arms, respectively). Non-hematologicaltoxicities were superimposable in the two arm, while DES-chemo-therapywas more myelotoxic. CONCLUSIONS:: This trial confirms that chemotherapy preceded by estrogenicrecruitment is still in an experimental phase and that, at present,it has no role in clinical practice. Further research is neededto test the possibility of combining different mitogens in thelight of new information about breast cancer cell growth. estrogenic recruitment, metastatic breast cancer     

Bicalutamide monotherapy versus flutamide plus goserelin in prostate cancer: updated results of a multicentric trial

OBJECTIVES: To compare the efficacy of bicalutamide monotherapy to maximal androgen blockade in advanced prostatic cancer. PATIENTS AND METHODS: Previously untreated patients with histologically proven stage C or D (American Urological Association Staging System) disease were randomly allocated to either bicalutamide (B) or goserelin plus flutamide (G+F). After disease progression, patients treated with B were assigned to castration. The primary endpoint for this trial was overall survival. Prostate cancer-specific survival and progression were included among secondary endpoints. RESULTS: In total 108 patients received B and 112 received G+F. At a median follow-up time of 54 months (range 1-89), 151 patients progressed and 113 died. There was no significant difference in the duration of either progression-free or overall survival. Hazards of progression, death and cancer-specific death, corrected by disease stage, tumor grade and baseline PSA level, showed that patients initially assigned to B had a higher risk of progression but a comparable risk of death and cancer-specific death with the exception of patients with G3 tumors who had an increased risk of death). CONCLUSIONS: In patients with well or moderately well differentiated tumors, B monotherapy followed by castration may offer the same survival chance as maximal androgen deprivation. In those patients it thus represents a reasonable choice that can avoid the side effects of androgen deprivation for considerable periods of time.     

Enterolactone in breast cyst fluid: correlation with EGF and breast cancer risk

The purpose of our study was to investigate whether enterolactone does accumulate into breast cyst fluid and whether it correlates with breast cancer risk. We included 258 women who had at least one cyst aspiration and known intracystic cation and epidermal growth factor (EGF) concentration values. For 191 of such women serum aliquots were also available. The median value of serum enterolactone was 17 nM/l (range 1–140 nM/l). The median intracystic level of enterolactone was much higher (63 nM/l, range 0–872 nM/l) and was significantly higher in type I cysts (p = 0.000). This cyst type contained also significantly higher levels of EGF (p = 0.000). A direct relationship was found between serum and cyst fluid enterolactone levels (p = 0.000) and between cyst enterolactone and EGF levels (p = 0.03), the latter correlation being evident especially in type II cysts. Twelve patients in the cohort of women were found to have developed a breast cancer. After univariate analysis breast cancer risk was associated with cyst type and especially with EGF concentration. No association was evident for enterolactone concentration. However, enterolactone concentration appeared to significantly decrease the risk of patients with high EGF concentrations. Our results show that enterolactone does accumulate in breast cysts, and that it modulates the risk related to the intracystic level of EGF, which is confirmed to be a strong predictor of breast cancer risk.     

High-dose cyclophosphamide followed by autografting can improve the outcome of relapsed or resistant non-Hodgkin's lymphomas with involved or hypoplastic bone marrow

We report our experience of high-dose cyclophosphamide (HDCY) followed by high-dose therapy (HDT) and peripheral blood progenitor cell (PBPC) autografting in patients with diffuse, intermediate and high-grade non-Hodgkin's lymphomas who have failed conventional treatment. From 1991 to 1996, 54 consecutive patients pre-treated with a median of two chemotherapy lines entered the study. Eighteen patients (33%) were still responders to conventional chemotherapy (sensitive relapse), and 20 patients (37%) were in partial response (PR) after chemotherapy (CT). Sixteen patients (30%) were resistant to conventional CT either at presentation (non responder) or in relapse (resistant relapse). Thirty-nine patients had bone marrow involved by disease and fifteen had an hypoplastic marrow following conventional treatment. Patients received HDCY (7gr/m2) and G-CSF or GM-CSF in order to collect PBPC. Median collected CD34+ cells was 12.3 x 10(6)/Kg (range 0.7-197). After HDT (BEAM or Melphalan + TBI) 50 patients underwent PBPC autografting. According to intention to treat, 44 (81%) of 54 patients achieved complete remission (CR) (50% after HDCY and 31% after HDT). Procedure related death occurred in 6 patients (11%), one after HDCY and 5 after autografting. Twenty-nine (66%) of 44 patients are still in CR, 7 to 63 months (median 27 months) after the procedure. Three-year probability of survival, disease-free survival and progression-free survival are 63%, 64% and 52% respectively. In conclusion, HDCY is an effective procedure not only in mobilizing PBPC, but also in reducing tumour burden. HDT with PBPC support may further improve the outcome in this category of high-risk non-Hodgkin's lymphomas.     

Adjuvant immunochemotherapy in colorectal cancer Dukes C

The initial aim of the present study was to verify in a randomized trial whether the addition of Levamisole, an immunomodulator, could increase the effectiveness of postoperative chemotherapy (MeCCNU + 5-FU) in Dukes C colorectal cancer patients. After entering 29 consecutive patients, the poor results of most studies of adjuvant therapy in colorectal cancer prompted an early end to patient accrual. After 8 years, the lack of significance in survival (48.9 versus 37.3%) and disease-free survival (50 versus 38.8%) between the two treatment arms rules out any improvement associated with Levamisole administration.