Gemcitabine and oxaliplatin combination: a multicenter phase II trial in unfit patients with locally advanced or metastatic urothelial cancer.

BACKGROUND: Up to 50% of patients with bladder cancer cannot be treated with cisplatin because they are considered unfit due to poor renal function. Gemcitabine and oxaliplatin are active, nonnephrotoxic therapies with nonoverlapping toxicity profiles that provide an alternative therapy for this group of patients. PATIENTS AND METHODS: In a multicenter study, patients received gemcitabine 1200 mg/m(2) on days 1 and 8 and oxaliplatin 100 mg/m(2) on day 8 every 21 days. Eligible criteria were creatinine clearance >30 ml/min and/or Eastern Cooperative Oncology Group (ECOG) performance status of two or less. RESULTS: Forty-six patients were assessable for response and toxicity. Median age was 69 years (range 52-85), median ECOG two (range 0-2). Median number of metastatic sites was 2 (range 1-6). Median creatinine clearance was 50.73 ml/min (range 30-87). A total of 187 cycles were given with a median of 5 (range 1-6). Hematological toxicity was mild with grade 3-4 peripherical neuropathy occurring in 4% of patients. Overall response rate was 48% (three complete response, 19 partial response, seven stable disease and 17 progressive disease). Median time to disease progression was 5 months. CONCLUSION: Gemcitabine-oxaliplatin is an active and tolerable combination with response rate that merits further study in patients with impaired renal function but good performance status.

Feasiblity study of gemcitabine and cisplatin administered every two weeks in patients with advanced urothelial tumors and impaired renal function

OBJECTIVES: Cisplatin-based combination chemotherapy is the mainstay of treatment for advanced bladder cancer. However, full doses of cisplatin cannot be delivered in patients with impaired renal function. Our aim was to prove the feasibility of a gemcitabine and low-dose cisplatin regimen, delivered every two weeks in patients with impaired renal function. MATERIAL AND METHODS: Patients with locally advanced or metastatic bladder cancer with creatinine clearance between 35-60 ml/min received gemcitabine 2500 mg/m2 and cisplatin 35 mg/m2 on day 1, every 14 days. RESULTS: Between January 2004 and March 2005, 17 patients were treated. Mean creatinine clearance was 47.8 ml/min (range: 37-59 ml/min). Four patients had previously received chemotherapy with gemcitabine and/ or platinum. Median number of cycles per patient was 5 (1-13). No patient developed renal toxicity or worsening of renal function. Main toxicities were (grade 3/4): Anemia 2/1; leucopenia: 1/2; trombopenia 1/1. There was one toxic death related to metabolic acidosis, secondary to vomiting. Among 16 patients evaluable for response, we observed one complete response, 7 partial responses (ORR: 53.3%; IC 95%: 28.1-78.5%), 6 stabilizations (37.5%) and 2 progressions (12.5%). CONCLUSIONS: Gemcitabine and low-dose cisplatin is a safe and feasible combination in patients with poor renal function. Response rates seem similar to those previously described with standard schedules of this combination (AU)

Activation of nuclear factor-kappa B is linked to resistance to neoadjuvant chemotherapy in breast cancer patients.

The nuclear factor (NF)-kappaB system is a promising anticancer target due to its role in oncogenesis and chemoresistance in preclinical models. To provide evidence in a clinical setting on the role of NF-kappaB in breast cancer, we aimed to study the value of basal NF-kappaB/p65 in predicting resistance to neoadjuvant chemotherapy, and to characterise the pharmacodynamic changes in NF-kappaB/p65 expression following chemotherapy in patients with locally advanced breast cancer. Pre- and post-chemotherapy tumour specimens from 51 breast cancer patients treated with anthracycline- and/or taxane-containing neoadjuvant chemotherapy were assayed by immunohistochemistry for NF-kappaB/p65 subcellular expression. We studied NF-kappaB/p65, a well-characterised member of the NF-kappaB family that undergoes nuclear translocation when NF-kappaB is activated. Activation of NF-kappaB (i.e. nuclear NF-kappaB/p65 staining in pre-therapy specimens) was linked to chemoresistance. Patients with NF-kappaB/p65 nuclear staining in pre-treatment samples had a 20% clinical response rate, while patients with undetected nuclear staining had a 91% response rate to chemotherapy (P = 0.002). Notably, four patients achieved a complete histological response and none of them had pre-treatment NF-kappaB/p65 nuclear staining. Moreover, the number of patients with NF-kappaB/p65 activation increased after chemotherapy exposure. It is concluded that NF-kappaB/p65 activation assayed by immunohistochemistry is a predictive factor of resistance to neoadjuvant chemotherapy in breast cancer patients. Moreover, NF-kappaB activation was inducible following chemotherapy in a proportion of breast cancer patients. These novel clinical findings strengthen the rationale for the use of NF-kappaB inhibitors to prevent or overcome chemoresistance in breast cancer.

Phase II study of estramustine and vinorelbine in hormone-refractory prostate carcinoma patients.

The purpose of this study was to evaluate the antitumor activity of vinorelbine and oral estramustine phosphate in patients with metastatic, hormone-refractory prostate cancer. We evaluated the activity of this association using the following schedule: estramustine phosphate 600 mg/m2/day orally days 1-42 and vinorelbine 25 mg/m1 days 1, 8, 22, 29 cycles repeated every 56 days. Twenty-five patients were included in the study, 24 being evaluable for response and 25 for toxicity. Out of 5 patients with measurable disease, none had an objective response. Of the 24 assessable patients with bone metastases, 9 patients had a > or = 65% decline in pretreatment prostate-specific antigen (PSA) level, stable disease was observed in 10 and 5 patients progressed. Toxicities were minimal. Anemia was observed in 5 patients, alopecia in 4 and nausea and vomiting was observed in 6 patients. Anorexia and weight loss of more than 10% were observed in 2 patients. This combination is active and well tolerated in hormone-resistant prostate cancer. These results support the therapeutic strategy of combining agents that impair microtubule function.

Randomised double-blind study comparing tropisetron alone and in combination with dexamethasone in the prevention of acute and delayed cisplatin-induced emesis.

In a randomised, double-blind and parallel-design multicentre study, 282 chemotherapy-naive cancer patients received tropisetron 5 mg intravenously (i.v.) before high-dose cisplatin on day 1, and oral tropisetron 5 mg daily on days 2-6, in combination with either placebo (n = 143) or dexamethasone (n = 135), given i.v. on day 1 and orally on days 2-6. Complete protection from acute vomiting/nausea was achieved in 76.3%/79.3% of patients receiving the combination and in 55.2%/61.5% of those receiving tropisetron alone. Complete protection on days 2-6 from delayed vomiting/nausea was obtained in 60%/60% and 39.2%/40.6%, respectively. Tropisetron in combination with dexamethasone is safe and more effective than tropisetron alone in the prevention of both acute and delayed cisplatin-induced emesis.

Vegetable and fruit intake and the risk of lung cancer in women in Barcelona, Spain.

A case-control study on women was carried out in Barcelona, Spain, to investigate the relationship of lung cancer with the intake of vegetables, fruits and some foods of animal origin. The study included 103 cases and 206 controls matched by age and residence. Diet intake was assessed by means of a food frequency questionnaire. A reduction in risk, adjusted for smoking habit, was found for the intake of yellow/orange vegetables (mainly carrots) and tomatoes. The odds ratio (OR) and 95% confidence interval (CI) for the highest versus lowest tertile of intake were 0.37 (0.19-0.74) for yellow/orange vegetables and 0.45 (0.22-0.91) for tomatoes; both had a significant inverse trend. A tendency to a reduction in risk of lung cancer with increased intake was observed for all vegetables, leafy green vegetables, dark green vegetables and cruciferous, but these associations did not reach statistical significance. No association with lung cancer was found for the intake of fruits or foods of animal origin rich in retinol. Similar patterns were observed for women who never smoked and when the analysis was restricted to adenocarcinoma.

Anal carcinoma: a 14 year experience.

A retrospective analysis of 20 patients with anal carcinoma treated at Hospital del Mar (Barcelona) from 1982 to 1995 was performed to evaluate clinical and pathological characteristics. This subset represents 2.1% of all the colon and rectum cancers registered in the same period. The mean age was 74 years (42-92), the female to male ratio was 1.5:1. The most frequent site was anal canal (80%) and the histological type was squamous cell and basaloid carcinomas in all cases. Five aged patients were not treated. Twelve patients were primary treated by abdominal perineal resection, 2 patients by radiotherapy and one by a local excision. The prognosis of 8 patients treated with palliative surgery was poor and none survived 30 months after surgery. In contrast, 4 of 5 patients are alive after radical surgery with a minimum 5 year follow-up. Two patients treated with radiotherapy are disease free at 7 and 13 months after treatment. The incidence of anal carcinoma is low, but our experience shows that it is diagnosed at an advanced stage and surgery is not always successful. Radiotherapy with or without chemotherapy, is an effective alternative.

Phase II study of Mitonafide in advanced and relapsed colorectal cancer.

BACKGROUND: This study investigated the antitumoral activity in colorectal cancer and toxicity of a 5-day continuous infusion of a new cytostatic agent, Mitonafide, that had previously shown to be neurotoxic when administered as a short daily x 5 days infusion. PATIENTS AND METHODS: Seventeen chemotherapy-naive patients with advanced or relapsed colorectal cancer and measurable disease entered the study. All but one received a 120-hour (5-day) continuous infusion of Mitonafide at a starting dose of 200 mg/m2/day every 3 weeks. Toxicity evaluation was performed after each course and response assessment every 2 courses using the standard World Health Organization (WHO) criteria completed by the "Mini-mental state" test for cognitive status examination. RESULTS: Sixteen patients received a total of 41 courses of Mitonafide which resulted to be severely myelotoxic. In total, 13/16 patients had WHO grade 3-4 neutropenia, 7 of them with infection, and the treatment had to be stopped in 3 patients after only 1 course due to excessive toxicity. No central nervous system toxicity was observed. No objective responses were evidenced. CONCLUSIONS: At the dose and schedule of administration used, Mitonafide is not active in colorectal cancer and induces severe myelotoxicity thus not deserving further studies in this indication.

Sequential methotrexate, 5-fluorouracil (5-FU), and high dose leucovorin versus 5-FU and high dose leucovorin versus 5-FU alone for advanced colorectal cancer. A multi-institutional randomized trial.

BACKGROUND: The primary objective of this study was to compare the single-biochemical modulation of 5-fluorouracil (5-FU) and leucovorin with that of the double-biochemical modulation of methotrexate and leucovorin. Because of the Martin et al. study in which an experimental model showed similar effects of 5-FU at maximum tolerated doses to the modulation with leucovorin at standard doses, a third treatment arm of 5-FU alone was also studied. METHODS: A randomized trial was performed using a 500-mg/m2 intravenous (i.v.) 1-hour infusion of methotrexate, and 12 hours later, a 600-mg/m2 i.v. bolus of 5-FU plus a 200-mg/m2 i.v. 1-hour infusion of leucovorin (MFL) every 2 weeks versus 5-FU plus leucovorin at an equal dose and schedule (FL), versus a 1200-mg/m2 i.v. dose of 5-FU every 2 weeks. Of 186 patients included in the study, 178 were evaluable. RESULTS: In a preliminary analysis with 94 evaluable patients, two significant statistical differences were shown. First, the toxicity rate of the 5-FU--alone (F) treatment arm was higher than that of the other arms (MFL vs. F, P = 0.0002; FL vs. F, P = 0.00001). Second, the median survival was worse in the F treatment arm with a rate of 12.6 months for the MFL and FL arms and 7.5 months for the F arm (P < 0.05). Considering these results, the F treatment arm was discontinued. The final results included 70 evaluable patients for MFL and 74 patients for FL. No difference was found in the distribution of prognostic factors. The response rates were 25.7% for MFL (95% CI, 16-37.5) and 14.8% for FL (95% CI, 7.6-25), (P = 0.1). The median survival was 14.3 months for patients treated with MFL and 12.3 months for those treated with FL. The hematologic toxicity was mild, with no grade 3/4 leukopenia in either treatment arm. The major nonhematologic toxicity in the MFL and FL treatment arms was ocular; nongrade 3/4 diarrhea also was observed. CONCLUSIONS: The results of MFL double-biochemical modulation failed to show a significant statistical difference from that of single-biochemical modulation for this dose and schedule.

Lung cancer and cigarette smoking in women: a case-control study in Barcelona (Spain).

A case-control study on lung cancer and the habit of cigarette smoking was carried out in Barcelona (Spain). Cases were 103 women newly diagnosed with primary lung cancer in 10 hospitals from the study area. Histologic confirmation was given in 101 cases, of which 53 were adenocarcinoma, 19 squamous-cell carcinoma, 9 small-cell carcinoma and 20 other types. Two controls per case were selected, matched by age, residence and hospital. Compared with the never-smokers, the odds ratios (OR), with corresponding 95% confidence intervals (CI), were 1.61 (0.4 to 6.9) for ex-smokers and 3.61 (1.6 to 8.3) for current smokers. The risk of lung cancer showed a good dose-response relationship with duration of the habit, average number of cigarettes smoked daily and cumulative cigarette consumption. The risk of lung cancer increased by 62% for each 10 pack-years. Depth of inhalation also showed a remarkable effect, independently of the intensity of the habit. Although mortality and incidence rates of lung cancer among women in Spain are lower than in other developed countries, the risk of lung cancer is that which would be expected according to the pattern of the smoking habit in Spanish women.

Fibrolamellar hepatic tumor with neurosecretory features and systemic deposition of AA amyloid.

A 28-year-old man presented with left cervical lymph node metastases and a 7-cm mass in the left lobe of the liver. Biopsy material from both sites revealed a fibrolamellar hepatocarcinoma (FLHC) with immunocytochemical and ultrastructural evidence of neurosecretory differentiation. The patient refused treatment. He died 6 years after the onset of symptoms with grade IV coma and bilateral bronchopneumonia. Postmortem examination disclosed persistent neoplastic disease in the liver and left lateral cervical lymph nodes as well as widespread deposition of AA amyloid in tumor stroma and in blood vessel walls of many tissues but mainly in the kidney, gastrointestinal tract, and heart. This appears to be the first report documenting the association of FLHC and amyloid deposition in the English literature.

[Acquired immunodeficiency syndrome and T-cell non-Hodgkin's lymphoma]. / Síndrome de inmunodeficiencia adquirida y linfoma no hodgkiniano de células T.

The clinical observation of a 40 years old male presenting acquired immune deficiency syndrome and T-cell non Hodgkin's lymphoma is presented. The patient was treated with COMET-A regimen (cyclophosphamide, vincristine, methotrexate, etoposide and cytarabine) and a complete remission was obtained.