ABSTRACT: PurposeOrgan preservation has been investigated in patients (p) with infiltrating transitional cell carcinoma (TCC) of the bladder
over the past decade as an alternative to radical cystectomy. This is a trimodal schedule study, including transurethral resection
of bladder tumor (TURB), neoadjuvant chemotherapy and concomitant radiochemotherapy (RTC).
Patients and methodsFrom April 1996 until August 2005, 29 evaluable patients (p) with T2-T3NXM0 bladder cancer were enrolled. After a transurethral
resection of bladder tumor (TURB), we administered 2 cycles of induction chemotherapy with CMV (15 p) or Gemcitabine-Cisplatin
(14 p) followed by radiotherapy 45 Gy 1.8 Gy/fraction and two cycles of concomitant cisplatin 70 mg/m2. 2–3 weeks later, a cystoscopy with tumor-site biopsy was performed. If complete histological response, p were treated with
consolidation radiotherapy until 64.8 Gy. For p with residual or recurrent tumor, cystectomy was performed.
ResultsWe included 28 men and 1 women (median age 63, range 39–72 years) with PS (ECOG) 0–1. The stage was: 21 p T2; 6 p T3a; and
2 p T3b. Toxicity was higher in CMV compared with Gem-Cis: grade 3/4 neutropenia 4/15 (26%) vs 1/14 (7%); febrile neutropenia
3/15 (20%) vs 1/14 (7%); grade 3/4 trombocytopenia 2/15 (13%) vs 1/14 (7%). Toxicities with concomitant RCT were low-moderate:
urocystitis (26%) and enteritis (18%). Response: microscopically complete TURB was obtained in 20 p (69%), but not in 9 p
(31%) (7 microscopic, and 2 macroscopic residual tumor). We found a complete histologic response after induction RCT in 25
p (86%). After a median follow-up of 69.4 months (m) (range: 8–97.7), there were 8 deaths, with a overall survival of 72%.
Furthermore 14 of 29 p (48%) were alive with intact bladder, and median survival time with intact bladder was 63.6 m (50.1–77.2);
were predictive of best outcome T2 stage vs T3 (p<0.0001), and complete histologic resection in initial TURB vs residual tumor
ConclusionsCombined treatment provide high response rates and can be offered as an alternative option to radical cystectomy in selected
patients with TCC. Patients with T2 stage and complete histologic resection in initial TURB had the best outcome.
Clinical and Translational Oncology 04/2012; 8(12):903-911. · 1.33 Impact Factor
ABSTRACT: To determine the recommended dose, cardiac safety, and antitumor activity of nonpegylated liposomal doxorubicin (TLC-D99), paclitaxel, and the anti-HER-2 monoclonal antibody trastuzumab in patients with HER-2-overexpressing locally advanced nonoperable breast cancer (LABC) and metastatic breast cancer (MBC).
Women with measurable, previously untreated, HER-2-overexpressing LABC and MBC with a baseline left ventricular ejection fraction (LVEF) >50% received weekly trastuzumab in combination with escalating doses of weekly paclitaxel and TLC-D99 every 3 weeks for 6 cycles. LVEF monitoring was done every 3 weeks for the first 18 weeks and every 8 weeks thereafter.
Sixty-nine patients participated, 15 in the dose escalating part and 54 at the recommended phase II dose (28 patients with LABC and 26 patients with MBC). The recommended doses of TLC-D99 and paclitaxel were 50 mg/m(2) every 3 weeks and 80 mg/m(2)/wk, respectively. Twelve (17%) patients developed asymptomatic declines in LVEF. In 8 of these patients, LVEF recovered to >or=50% after a median time of 9 weeks (range, 3-38 weeks). In the rest of patients, LVEF ranged from 44% to 49%. No patients developed symptomatic cardiac heart failure. The overall response rate was 98.1% (95% confidence interval, 90.1-99.9) with a median time to progression not reached in LABC and of 22.1 months (95% confidence interval, 16.4-46.3) in MBC patients.
Nonpegylated doxorubicin, paclitaxel, and trastuzumab combination is safe, does not result in clinically manifest cardiac toxicity, and has a high rate of durable responses in HER-2-overexpressing breast cancer patients. Further exploration of this combination is warranted.
Clinical Cancer Research 02/2009; 15(1):307-14. · 7.74 Impact Factor
ABSTRACT: We conducted a phase II trial to evaluate the efficacy and toxicity of a combination consisting of second-line docetaxel and gemcitabine in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy.
Eligibility criteria: histologically confirmed advanced NSCLC with progressive disease to platinum-based chemotherapy, ECOG performance status (PS) 0 or 1, and adequate kidney, liver and bone marrow function. Treatment consisted of docetaxel 36 mg/m(2) i.v. over 60 min followed by gemcitabine 1000 mg/m(2) i.v. over 30 min on days 1 and 8 of each 3-week cycle for a planned six cycles or unacceptable toxicity.
Of the 52 patients enrolled, 50 were evaluable for response and toxicity. The mean age was 59 years (range 42-79), 46 male and 4 female. Histology subtypes were: adenocarcinoma 26 patients, bronchioloalveolar 1 patient, large cell carcinoma 5 patients, and squamous cell carcinoma 18 patients. Thirty-eight patients had ECOG PS 1 and 12 patients had PS 0. The median number of cycles administered was four (range 2-6). The overall response rate was 28%. The median follow-up was 9 months (range 5-34 months). The median survival time (MST) was 8.2 months (95% CI, 4-12%), and the 1-year survival was 25%. The median progression-free survival was 4.4 months (95% CI, 2-6%). In the Cox regression model, survival was only significantly affected by the PS. The median survival in patients with PS 0 was 17.8 months (95% CI, 18.8-21.8%) compared with a median survival for patients with PS 1 of 6.1 months (95% CI, 4.1-8.2%) (P=0.0057). Toxicity: three patients had grade 3 anemia, three patients had grade 3 thrombocytopenia, four patients had grade 3 neutropenia and only one patient developed grade 4 febrile neutropenia. Non-hematologic toxicity was also mild; the most frequent was asthenia, with grade 3 in eight patients (16%), and one patient with grade 4.
This regimen of docetaxel in combination with gemcitabine in advanced second-line NSCLC is an active and safe regimen.
Lung Cancer 06/2007; 56(2):255-62. · 3.43 Impact Factor
ABSTRACT: This phase II study evaluated the efficacy and toxicity of weekly cisplatin along with concomitant boost accelerated radiation regimen in patients with locally advanced unresectable head and neck carcinoma.
A total of 94 patients (median age, 58 years) with UICC stage III (n = 19) and IV (n = 75) cancer of the oropharynx, larynx, hypopharynx and oral cavity were included. Patients received radiotherapy with a concomitant boost scheme (1.8 Gy on days 1-40 and 1.5 Gy boost on days 25-40 with a total dose of 72 Gy) and concurrent cisplatin, 40 mg/m(2) weekly, for the first 4 weeks.
Most patients (95%) received both radiation and chemotherapy according to protocol. Toxicity was manageable with grade III mucositis and pharyngeal-oesophageal toxicity in 85 and 50% of patients, respectively. Haematological toxicity was mild. Four patients (4%) died due to complications. With a median follow of 41 months, median overall survival and time to progression were 27 and 25 months, respectively. The estimated overall survival at 4 years was 41%.
Concomitant boost accelerated radiation plus concurrent weekly cisplatin is a feasible schedule in patients with locally advanced unresectable head and neck carcinoma, with acceptable toxicity and survival data.
Radiotherapy and Oncology 05/2006; 79(1):34-8. · 5.58 Impact Factor
ABSTRACT: Several HLA alleles are associated with susceptibility or protection in breast cancer. The particular allele varies depending on the geographical region. A study in a small group of Spanish patients using serological methods found an association with HLA-B7. We undertook a larger study in southern Spain using molecular biology techniques.
Genotype variants of HLA class I and II were typed by PCR-SSP in 132 breast cancer patients and 382 healthy controls.
The frequency of the HLA-B7 allele was increased in the patients compared to the controls (P=0.0019; 95% confidence interval, 1.337-3.409, relative risk=2.135). Bonferroni correction of the P showed it was still significant (P(c)=0.0285).
These results support previous suggestions that HLA-B7 is associated with the development of breast cancer in our area.
Immunology Letters 12/2005; 101(2):223-5. · 2.53 Impact Factor
ABSTRACT: This phase II study evaluates the activity of temozolomide and cisplatin administered before radiation therapy in newly diagnosed glioblastoma multiforme patients, in terms of response, time to progression and survival.
Forty patients with measurable disease after surgery, a Karnofsky status > 60, and Barthel Index > 10 were included. They were treated with three cycles of temozolomide 200 mg/m2/day for 5 days and cisplatin 100 mg/m2 on day 1. Conventional focal radiation therapy to 60 Gy was administered after response evaluation.
Three patients were not evaluable for central reviewed response but all 40 were evaluable for toxicity, time to progression and survival. Objective responses by Macdonald criteria on an intent to treat basis were 45% including complete response in three patients (7.5%), and partial response in 15 patients (37.5%). Responses were seen in biopsy-only patients (33.4%) as well as in partial surgery patients (52%). Median survival for all patients was 12.5 months. Biopsy-only patients had a median survival of 12.8 months. Grade 3 to 4 neutropenia was the most important toxicity, and occurred in 37.5% of patients. A delay in 18.2% and a dose reduction in 9.6% of cycles were necessary due to myelosuppression on day 28. Two patients had neutropenic fever resulting in one treatment-related death. Eighty-two percent of patients received radiotherapy.
This regimen has significant activity, as it induces objective responses even in biopsy-only patients, appearing to improve their median survival. A better combination schedule is needed to improve the toxicity profile.
Journal of Neuro-Oncology 01/2005; 70(3):359-69. · 3.21 Impact Factor
ABSTRACT: Manual para el uso de los centros de autoacceso, propuesta metodológica para el autoprendizaje de lenguas extranjeras.