Paclitaxel and cisplatin in advanced or recurrent carcinoma of the endometrium: long-term results of a phase II multicenter study

OBJECTIVES: Both paclitaxel and cisplatin have moderate activity in patients with metastatic or recurrent carcinoma of the endometrium, and the combination of these two agents has shown activity in a variety of solid tumors. We administered this combination to patients with metastatic or recurrent carcinoma of the endometrium to evaluate its activity and to define its toxicity. METHODS: Twenty-four consecutive patients were treated on an outpatient basis with paclitaxel 175 mg/m(2) administered intravenously over a 3-h period followed by cisplatin 75 mg/m(2) administered intravenously with granulocyte colony-stimulating factor (G-CSF) support. The chemotherapy was repeated every 3 weeks for a maximum of six courses. RESULTS: Sixteen patients (67%; 95% confidence interval, 45-84%) achieved an objective response, including seven complete responses and nine partial responses. The median duration of response was 7 months, and the median times to progression and survival for all patients were 8.4 and 17.6 months, respectively. Some degree of neurotoxicity occurred in 44% of patients. Grade 3 or 4 toxicity included granulocytopenia in 22% of patients and peripheral neuropathy in 9%. CONCLUSION: The combination of paclitaxel with cisplatin with G-CSF support appears active in patients with metastatic or recurrent carcinoma of the endometrium. The significant incidence of neurotoxicity is of concern and alternative methods of administration of the two agents could be evaluated.     

First line combination chemotherapy with docetaxel and vinorelbine in advanced breast cancer. A phase II study

We evaluated the efficacy and tolerance of the combination of docetaxel and vinorelbine as first line treatment in metastatic breast cancer (MBC). These agents have different mechanisms of action and both are active in advanced breast cancer. Thirty-nine chemotherapy-naive for metastatic disease patients were treated on an out-patient basis with vinorelbine 20 mg/m2 i.v. on days 1 and 8 and docetaxel 85 mg/m2 i.v. on day 8, every 3 weeks. Twenty-one (53.8%) patients had locoregional disease, 30 (76.9%) had distant metastases and 20 (51.3%) had visceral metastases. The intent-to-treat objective response rate (RR) was 48.75% (19 out of 39 patients; 95% confidence interval (CI), 32.4% to 65.2%). Four patients (10.25%) achieved a complete response (CR) (95% CI, 2.9% to 24.2%) and 15 (38.5%) a partial response (PR) (95% CI, 23.4% to 55.4%). The median duration of response was 4 months, the median time to progression (TTP) was 6 months and the median survival-time was 11.3 months. Grade 3 and/or 4 (3/4) anemia and thrombocytopenia occurred in 7.7% and 5.1% of patients, respectively. Twelve (30.7%) patients developed grade 3/4 neutropenia and 7 (17.9 %) were complicated with fever. Grade 3/4 diarrhea, nausea-vomiting, fatigue and constipation were not a problem. Alopecia was universal. Grade 3/4 neurotoxicity was evident in 2.6% of patients. None of the patients developed allergic reaction or fluid retention. There was one treatment-related death due to grade 4 neutropenia and sepsis. CONCLUSION: This combination of docetaxel and vinorelbine, a non-anthracycline-containing regimen, is a moderately effective regimen for the treatment of chemotherapy-naive breast cancer patients with metastases, causing only mild to moderate toxicity.     

Treatment of Waldenstrom's macroglobulinemia with thalidomide.

PURPOSE: We performed a prospective phase II study to assess the activity of thalidomide in patients with Waldenstrom's macroglobulinemia (WM). PATIENTS AND METHODS: Twenty patients with WM were treated with thalidomide at a starting dose of 200 mg daily with dose escalation in 200-mg increments every 14 days as tolerated to a maximum of 600 mg. All patients were symptomatic, their median age was 74 years, and 10 patients were previously untreated. RESULTS: On an intent-to-treat basis, five (25%) of 20 patients achieved a partial response after treatment. Responses occurred in three of 10 previously untreated and in two of 10 pretreated patients. None of the patients treated during refractory relapse or with disease duration exceeding 2 years responded to thalidomide. Time to response was short, ranging between 0.8 months to 2.8 months. Adverse effects were common but reversible and consisted primarily of constipation, somnolence, fatigue, and mood changes. The daily dose of thalidomide was escalated to 600 mg in only five patients (25%), and in seven patients (35%), this agent was discontinued within 2 months because of intolerance. CONCLUSION: Our data indicate that thalidomide has activity in WM but only low doses were tolerated in this elderly patient population. Confirmatory studies as well as studies that will combine thalidomide with chemotherapy or with rituximab may be relevant.     

Association of a rare form of testicular ectopia, a persistent Müllerian duct syndrome and a supernumerary ectopic epididymis

We report the first case of persistence of the Müllerian duct associated with transverse testicular ectopia and a supernumerary ectopic epididymis in the same hemiscrotum. The patient is a thirty-year-old man with azoospermia. Uterine and Fallopian tube structures were clearly recognizable within the Müllerian remnants. The ectopic supernumerary epididymis was detected at the lower pole of one of the two testicles and had to be removed surgically.     

Pars plana vitrectomy and silicone oil injection in proliferative diabetic retinopathy

A retrospective study is reported on 106 eyes with proliferative diabetic retinopathy, treated by vitrectomy and silicone oil injection. Indications were traction detachment in 91 eyes and nonclearing rebleeding in 15 eyes; 31 eyes had previously had vitrectomy. Anatomical success was obtained at the end surgery in 91 eyes, and after a minimum follow-up of 6 months in 68 eyes (64%). Functional results were as follows: satisfactory visual acuity (0.5–0.05) in 23 eyes (22%), ambulatory vision (0.03-CF) in 14 eyes (13%), HM-LP in 54 eyes (51%), and NLP in 15 eyes (14%). The functional results are limited by recurrent detachments due to characteristic reproliferations under the silicone bubble or by ischemic diabetic angiopathy in the attached retina. A positive effect of silicone oil is demonstrated in the reduction of preexisting or postoperatively new iris neovascularization and in preventing postoperative rebleeding.This study was supported by the Retinovit Foundation. Presented in part at the 1986 meeting of the Club Jules Gonin in Copenhagen, Denmark     

Squamous cell carcinoma of the renal pelvis presenting with a loin sinus

An unusual presentation of a renal pelvis squamous cell carcinoma is reported; a loin sinus with excessive pyorrhea was the only complaint of a man with a long history of renal calculus disease.     

Activity-rest stimulation protocol improves cardiac assistance in dynamic cardiomyoplasty.

OBJECTIVE: No data have ever been published regarding cardiac assistance in demand dynamic cardiomyoplasty (DDCMP). We tested the efficacy of the Doppler flow wire in measuring beat-to-beat aortic flow velocity and evaluating cardiac assistance in demand cardiomyoplasty patients. METHODS: The technique was tested in seven patients (M/F=6/1; age=57.1+/-6.2 years; atrial fibrillation/sinus rhythm=1/6; NYHA=1.4+/-0.5). Measurements were done using a 0.018inch peripheral Doppler flow wire advanced through a 5F arterial femoral sheath. Three 1-min periods with the stimulator off and three 1-min periods with clinical stimulation were recorded. We measured peak aortic flow velocity in all beats. Latissimus dorsi (LD) mechanogram was simultaneously recorded. RESULTS: Comparison between pre-operative and follow-up data showed significantly higher values of tetanic fusion frequency (TFF) and ejection fraction at follow-up, whereas mean NYHA class was significantly lower. Statistical analysis showed an increase in aortic flow velocity not only in assisted versus rest period, but also in assisted versus unassisted beats (8.42+/-6.98% and 7.55+/-3.07%). A linear correlation was found between the increase in flow velocity and LD wrap TFF (r(2)=0.53). CONCLUSIONS: In DDCMP, systolic assistance is significant and correlated to LD speed of contraction; demand stimulation protocol maintains muscle properties and increases muscle performance.     

Angiogenesis in Waldenström's Macroglobulinemia

Angiogenesis represents an essential step of disease progression in several hematological malignancies. In Waldenström's macroglobulinemia (WM) the bone marrow microvessel density is increased in 30%–40% of patients but seems to have no impact on survival. Angiogenic cytokines, such as angiogenin, vascular endothelial growth factor, and basic fibroblast growth factor are increased in the serum of WM or IgM-MGUS patients, while the ratio of angiopoietin-1/angiopoietin-2 is reduced in WM but not in IgM—monoclonal gammopathy of undetermined significance (MGUS). Angiogenin and angiopoietin-1/angiopoietin-2 ratio correlates with disease activity and clinical features of WM. Macrophage and mast-cell chemoattractants, such as macrophage inflammatory protein-1 alpha are also elevated in the serum of patients with WM, while both macrophages and mast cells that are increased in the WM microenvironment have angiogenic properties and participate in the angiogenesis process in several malignancies. This review summarizes all data available by November 2008 (end of literature search) for the role of angiogenesis in the biology of WM and its correlation with clinical and laboratory features of the disease.