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Roberto Díaz

Publications and source records attributed to Roberto Díaz.

7 recordsLinked to original sources
PubMed2006

Clinical predictors of severe toxicity in patients treated with combination chemotherapy with irinotecan and/or oxaliplatin for metastatic colorectal cancer: a single center experience.

INTRODUCTION: Little has been published regarding clinical predictors of severe toxicity in patients with metastatic colorectal cancer (CRC) treated with combination chemotherapy (CT) with oxaliplatin and/or irinotecan. MATERIAL AND METHODS: We analyzed retrospectively 142 patients treated between 1996 and 2004 in our center with these regimes with regards to grade 3-4 toxicity and overall survival (OS) rates. Köhne's prognostic classification could be applied in all patients. RESULTS: Köhne classification: good (54.2%), intermediate (26.8%), and poor prognosis (19%). 50.4% received irinotecan-based CT. Median number of cycles 6 with a total response rate of 38.9%. 23.2% stopped first-line CT due to toxicity. 50.7% suffered grade 3-4 toxicity: digestive (28.2%), hematologic (19.7%), and fatigue (25.4%). 7.7% episodes of neutropenic fever with 4.9% toxic deaths. 70.9% of grade 3-4 episodes occurred in the first four cycles. Median follow-up of 33.9 mo; median OS of 15.9 mo. For Köhne classification: good (20 mo), intermediate (15.8 mo), and poor (6.8 mo). Toxicity analysis: female sex and age > 70 yr predicted higher overall grade 3-4 toxicity, with no differences in CT efficacy; age > 70 yr and PS > 1 predicted higher grade 3-4 fatigue. No relationship could be found between baseline laboratory characteristics and higher toxicity, except baseline hemoglobin and grade 3-4 hematologic toxicity. CONCLUSIONS: Female and elderly patients have a higher grade 3-4 toxicity rate when treated with combination CT with oxaliplatin or irinotecan. Prognostic classifications such as Köhne's can help differentiate subgroups of patients who benefit little with the use of combination CT.

Adult↗
PubMed2005

Neoadjuvant cisplatin and etoposide, with or without tamoxifen, prior to radiotherapy in high-grade gliomas: a single-center experience.

Neoadjuvant chemotherapy (CT), prior to radical radiotherapy (RT), in the treatment of high-grade gliomas may offer several advantages over standard adjuvant CT. The addition of tamoxifen, which can circumvent P-glycoprotein (P-gp)-mediated chemo-resistance, also merits attention. We have evaluated the neoadjuvant regimen of cisplatin and etoposide after surgery of grade III-IV gliomas and prior to radical RT, with regard to response rates (RRs), overall survival (OS) and time to progression (TTP). The synergistic activity between etoposide and tamoxifen was also studied. Forty-four patients were included. CT regime: cisplatin 100 mg/m2 on day +1 and etoposide 100 mg/m2 on days +1 to +3 every 3 weeks for 3 cycles. The initial 24 were also treated with high-dose tamoxifen, 275 mg/m2 on days -3 to +3. An immunohistochemical analysis of P-gp, p53, vascular endothelial growth factor, Ki67 and bcl-2 was also performed. Median follow-up was 11.57 months. In the 16 patients with measurable disease after surgery, a RR of 12.5% was seen, with 37.5% of disease stabilizations and 31.25% of progressions. The median OS and TTP were 11.3 and 5.7 months. Excluding the three deaths possibly related to tamoxifen, grade 3-4 was low, mainly emesis. Favorable prognostic factors were age less than 60 years, extent of surgery, absence of measurable disease, and the absence of radiological necrosis and ring enhancement. Only high p53 expression was associated with better OS. We conclude that neoadjuvant cisplatin and etoposide is a feasible regime, although any real advantage over standard adjuvant CT is dubious. Short-course high-dose tamoxifen should not be used alongside primary CT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Analysis of prognostic factors and applicability of Kohne's prognostic groups in patients with metastatic colorectal cancer treated with first-line irinotecan or oxaliplatin-based chemotherapy.

BACKGROUND: The objective of this study was to analyze prognostic factors for survival and to assess the applicability of Kohne's classification in patients treated with irinotecan- or oxaliplatin-based first-line chemotherapy. PATIENTS AND METHODS: One hundred forty-two consecutive cases from a single center were retrospectively reviewed. Median patient age was 62 years. Sixty percent were men. Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0/1 in 88%. Primary tumor resection (PTR) was performed in 80.6% of patients who initially had stage IV disease. Chemotherapy consisted of fluoropyrimidines or raltitrexed plus irinotecan (50.5%), oxaliplatin (38.5%), or both (11%). Univariate and multivariate analyses for survival were performed using pretreatment patient characteristics. RESULTS: Median follow-up was 33.9 months and median overall survival was 15.9 months. Significantly unfavorable prognostic factors were PTR not being performed, disease involvement of >1 organ, liver metastases, undifferentiated histology, EGOG PS>1, increased serum carcinoembryonic antigen and cancer antigen 19.9 levels, hypoalbuminemia, leucocytosis, and elevated alkaline phosphatase and lactate dehydrogenase (LDH) levels. Only ECOG PS, PTR, increased LDH level, no hypoalbuminemia, and number of organs involved retained prognostic value in the multivariate analysis. The incidence and median survival for Kohne's prognostic groups were as follows: good (54.2%; 20 months), intermediate (26.8%; 15.7 months), and poor (19%; 6.8 months). For patients with stage IV disease at presentation, PTR was associated with a significantly longer survival, mainly in patients with an ECOG PS of 0/1. CONCLUSION: Eastern Cooperative Oncology Group PS, PTR, serum albumin, increased LDH levels, and organ involvement were the main prognostic indicators in our series. Kohne's prognostic groups, developed in the era of 5-fluorouracil treatment, also seem to be applicable to patients treated with combination chemotherapy. Primary tumor resection should always be considered, especially in patients with an ECOG PS of 0/1. However, the benefit of PTR and multiple-agent chemotherapy is questionable in patients with an ECOG PS of >1.

Aged↗
PubMed2003

rgr oncogene: activation by elimination of translational controls and mislocalization.

Previous studies have identified a novel oncogene, rgr, which has homology to the guanine nucleotide exchange factor (GEF) Ral guanine dissociation stimulator (RALGDS). To determine the mechanism of activation of rgr, the wild-type form was isolated. rgr is expressed physiologically at very low levels, due, at least in part, to a long 5'-untranslated region that contains eight AUGs, which inhibit translation of the main open reading frame. When these regulatory sequences are removed, the wild-type gene is expressed at high levels. An investigation of how this GEF could transform cells showed that RGR interacts with RAS, supporting its involvement as a RAS-GEF. Because RAL is localized mainly to the Golgi, the expression of the RGR protein was identified in RK13 cells, a cell line that expresses endogenous rgr. RGR localizes to endomembranes. To determine its location upon transformation, a green fluorescent protein-RGR fusion protein was used to track the movement of RGR. Increasing amounts of expression result in enhanced localization of RGR to the plasma membrane. These results indicate that rgr is activated when its tight translational controls are eliminated and increased expression allows its relocation to the plasma membrane, where efficient activation of RAS occurs.

3T3 Cells↗
PubMed2003

Analysis of clinical prognostic factors for survival and time to progression in patients with metastatic colorectal cancer treated with 5-fluorouracil-based chemotherapy.

Colorectal cancer (CRC) is one of the most common malignant tumors in adults. Twenty-five percent of patients are not amenable to surgical resection because they have locally advanced or metastatic disease. For these patients, median survival time is between 4 and 13 months, and chemotherapy is used mainly with palliative intent. We conducted this study to evaluate potential prognostic factors for time to progression and survival. A retrospective review of 91 patients with metastatic CRC treated with bolus 5-fluorouracil-based chemotherapy (Mayo Clinic schedule) was performed. Univariate and multivariate analyses of clinical prognostic factors were carried out. Median follow-up time was 53 months (range, 17-107 months). Median time to disease progression was 9.6 months, and median survival time was 15.4 months. Actuarial 5-year survival was 17%. In the univariate analyses, factors predictive of time to progression were visceral metastases, elevated alkaline phosphatase (AP) levels, performance status (PS), and elevated carcinoembryonic antigen (CEA) and CA 19-9 levels. Multivariate analyses confirmed the independent prognostic value of PS and AP levels. In the univariate analyses for survival, significant prognostic factors were visceral metastases, hypoalbuminemia, elevated lactate dehydrogenase levels, elevated AP levels, PS, and elevated CEA and CA 19-9 levels. In the multivariate analyses, only PS, elevated CEA and CA 19-9 levels, and liver involvement retained prognostic significance. This study confirms the prognostic value of PS for both time to progression and survival. AP levels are significantly related to time to progression. Additional factors influencing survival time are elevated tumor marker levels and the existence of liver metastases.

Adult↗