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Biomedical subjects

A Cervantes

Publications and source records attributed to A Cervantes.

At least 37 records · Page 2Linked to original sources
PubMed2002

Raltitrexed: current clinical status and future directions.

Raltitrexed ('Tomudex') monotherapy is a conveniently administered alternative to 5-fluorouracil (5-FU) in the first-line treatment of advanced colorectal cancer (CRC), and has single-agent activity in a variety of advanced solid tumours. Although both raltitrexed and 5-FU are thymidylate synthase inhibitors, raltitrexed has a specific mode of action and a toxicity profile distinct from 5-FU. The mechanism of action of raltitrexed is also completely different from that of oxaliplatin, irinotecan and other drugs with which it has been combined. These properties, together with preclinical data, suggested that combinations of raltitrexed with 5-FU, other chemotherapeutic agents, or radiotherapy could result in improved therapies for a variety of advanced solid tumours, including advanced CRC. This review outlines the appropriate management of patients treated with raltitrexed, whether as monotherapy or in combination, and discusses the preliminary results of combination studies with raltitrexed in a range of tumour types including advanced CRC, malignant mesothelioma, gastric, pancreatic, head and neck, and non-small-cell lung cancers. Of particular interest is the combination of raltitrexed and oxaliplatin, which has shown promising antitumour effects in first-line treatment of advanced CRC and malignant mesothelioma, a disease that is refractory to chemotherapy.

Antimetabolites, Antineoplastic↗
PubMed2001

Bleomycin, methotrexate, and CCNU in locally advanced or recurrent, inoperable, squamous-cell carcinoma of the vulva: an EORTC Gynaecological Cancer Cooperative Group Study. European Organization for Research and Treatment of Cancer.

OBJECTIVE: To investigate tumor response rate and treatment toxicity of a modified combination chemotherapy consisting of bleomycin (B), methotrexate (M), and CCNU (C) for patients with locally advanced, squamous-cell carcinoma of the vulva (not amenable to resection by standard radical vulvectomy) or recurrent disease (after incomplete resection). Tumor resectability was reassessed in patients who had responded to chemotherapy. METHODS: The regimen consisted of bleomycin 5 mg intramuscular (im) days 1-5, CCNU 40 mg per os (po) days 5-7, and methotrexate 15 mg po days 1 and 4 during the first week. During weeks 2-6 the patient was administered bleomycin 5 mg im days 1 and 4, and methotrexate 15 mg po on day 1 of the week. This 6-week cycle was repeated at 49-day intervals. RESULTS: Twenty-five eligible patients with a median age of 66 years (range, 39-82 years) were entered in this phase II trial. Twelve patients had primary locally advanced disease, 13 patients had a locoregional recurrence, and all received up to three BMC cycles. Two complete and twelve partial responses were observed (response rate, 56%; 95% confidence limits, 35-76%). The BMC regimen was associated with major hematological side effects and mild signs of bleomycin-related pulmonary toxicity. At a median follow-up of 8 months, 3 patients were alive, 18 had died due to malignant disease, 2 had died due to toxicity, and 2 had died due to intercurrent disease and unknown cause. The median progression-free survival was 4.8 months and the median survival was 7.8 months. The 1-year survival was 32% (95% confidence limits, 13-51%). CONCLUSION: The present data confirm the therapeutic activity of the BMC regimen in locoregionally advanced or recurrent squamous-cell carcinoma of the vulva. Following neoadjuvant chemotherapy, the overall response rate was 56%. BMC is an outpatient treatment that may play a role in the palliative therapy of advanced or recurrent vulva cancer.

Adult↗
PubMed2001

PCR-PRINS-FISH analysis of structurally abnormal sex chromosomes in eight patients with Turner phenotype.

According to cytogenetic analysis, about 50% of Turner individuals are 45,X. The remaining cases have a structurally abnormal X chromosome or are mosaics with a second cell line containing a normal or abnormal sex chromosome. In these mosaics, approximately 20% have a sex marker chromosome whose identity cannot usually be determined by classical cytogenetic methods, requiring the use of molecular techniques. Polymerase chain reaction (PCR), primed in situ labeling (PRINS), and fluorescence in situ hybridization (FISH) analyses were performed in 8 patients with Turner syndrome and 45,X mosaic karyotypes to determine the origin and structure of the marker chromosome in the second cell line. Our data showed that markers were Y-derived in 2 patients and X-derived in the remaining 6 patients. We were also able to determine the breakpoints in the two Y chromosomes. The use of cytogenetic and molecular techniques allowed us to establish unequivocally the origin, X or Y, of the marker chromosomes in the 8 patients with Turner phenotype. This study illustrates the power of resolution and utility of combined cytogenetic and molecular approaches in some clinical cases.

Adolescent↗
PubMed2001

Maternal race/ethnicity and twinning rates in the United States, 1989-1991.

OBJECTIVE: To utilize United States birth certificate data (years 1989-1991) to examine the effects of race/ethnicity on twinning rates. STUDY DESIGN: We used a database of birth certificate data for the United States (years 1989-1991) available on CD-ROM from the United States National Center for Health Statistics. This linked birth/infant death data set included a total of 12,036,234 birth records, of which 279,073 were twins. Excluded from the analysis were 15,086 twin birth records (5.4%) based upon previously described exclusion criteria. Statistical analysis included a series of univariate analyses to determine the rates of twinning between different racial/ethnic groups correlated with maternal age, education, marital status and place of birth. Comparisons were analyzed using the chi 2 test, with significance at P < .05. RESULTS: The overall twinning rate was 2.26%, with the lowest rate observed in the group denoted non-Hispanic other (1.67%) and highest among non-Hispanic blacks (2.69%). Twinning rates within various groups representing Hispanics ranged from 1.76% to 2.08%. The twinning rate was significantly higher among U.S.-born as compared to non-U.S.-born women (2.34% vs. 1.88%, P < .005) except for Puerto Ricans, Cubans and Central/South Americans, for whom the reverse was true. Women aged 35-39 had the highest twinning rate (3.05%), whereas women aged 15-19 had the lowest; that trend persisted in all racial/ethnic groups. The study showed a nonsignificant relationship between marital status or education and twinning rate. CONCLUSION: Race/ethnicity studies can be useful in designing programs that may maximize health outcomes of twins in a racially diverse population.

Adult↗
PubMed2000

Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer.

PURPOSE: In a previous study of treatment for advanced colorectal cancer, the LV5FU2 regimen, comprising leucovorin (LV) plus bolus and infusional fluorouracil (5FU) every 2 weeks, was superior to the standard North Central Cancer Treatment Group/Mayo Clinic 5-day bolus 5FU/LV regimen. This phase III study investigated the effect of combining oxaliplatin with LV5FU2, with progression-free survival as the primary end point. PATIENTS AND METHODS: Four hundred twenty previously untreated patients with measurable disease were randomized to receive a 2-hour infusion of LV (200 mg/m(2)/d) followed by a 5FU bolus (400 mg/m(2)/d) and 22-hour infusion (600 mg/m(2)/d) for 2 consecutive days every 2 weeks, either alone or together with oxaliplatin 85 mg/m(2) as a 2-hour infusion on day 1. RESULTS: Patients allocated to oxaliplatin plus LV5FU2 had significantly longer progression-free survival (median, 9.0 v 6.2 months; P =.0003) and better response rate (50.7% v 22.3%; P =.0001) when compared with the control arm. The improvement in overall survival did not reach significance (median, 16.2 v 14.7 months; P =. 12). LV5FU2 plus oxaliplatin gave higher frequencies of National Cancer Institute common toxicity criteria grade 3/4 neutropenia (41. 7% v 5.3% of patients), grade 3/4 diarrhea (11.9% v 5.3%), and grade 3 neurosensory toxicity (18.2% v 0%), but this did not result in impairment of quality of life (QoL). Survival without disease progression or deterioration in global health status was longer in patients allocated to oxaliplatin treatment (P =.004). CONCLUSION: The LV5FU2-oxaliplatin combination seems beneficial as first-line therapy in advanced colorectal cancer, demonstrating a prolonged progression-free survival with acceptable tolerability and maintenance of QoL.

Adenocarcinoma↗
PubMed2000

A mutation in the 5' non-high mobility group box region of the SRY gene in patients with Turner syndrome and Y mosaicism.

In Ullrich-Turner syndrome (UTS) patients, the presence of a Y-chromosome or Y-derived material has been documented in frequencies ranging from 4-61%. Mutations of SRY (testis-determining gene) constitute the cause of XY sex reversal in approximately 10-15% of females with pure gonadal dysgenesis. Most of these mutations have been described in the HMG (high mobility group) box of the gene, which is the region responsible for DNA binding and bending; however, various mutations outside the HMG box have been reported. We carried out molecular studies of the SRY gene in three patients with a UTS phenotype and bilateral streaks; two presented a 45,X/46,XY mosaic, and the third a Y marker chromosome. In two patients a missense mutation, S18N, was identified in the 5' non-HMG box region in DNA from blood and both streaks; this mutation was not identified in 75 normal males. Sequencing of the DNA region of interest was normal in the father and older brother of patient 1, demonstrating that in this patient the mutation was de novo. A previous report of a 46,XY patient with partial gonadal dysgenesis who presented the same mutation as our patients indicates the probable existence of a hot spot in this region of the SRY gene and strengthens the possibility that all gonadal dysgeneses constitute part of a spectrum of the same disorder. It also demonstrates that a single genetic abnormality can result in a wide range of phenotypic expression.

Adolescent↗
PubMed1999

Cyclophosphamide or ifosfamide in patients with advanced and/or recurrent endometrial carcinoma: a randomized phase II study of the EORTC Gynecological Cancer Cooperative Group.

UNLABELLED: Currently, available chemotherapy regimens for patients with advanced or recurrent endometrial cancer are generally not curative. Thus, there is a need to identify more active single agents in this disease. In this study patients pre-treated and not pre-treated with first line combination chemotherapy were entered into a randomized phase II study of either cyclophosphamide (CYCLO) or Ifosfamide (IFOS). PATIENTS AND METHOD: Sixty one eligible patients with recurrent or metastatic histologically proven, adenocarcinoma of the uterine corpus entered the study. The median age at entry was 62 (range 40-74) years. Twenty patients (33%) had prior hormonal treatment and 31 (51%) prior chemotherapy. CYCLO was given at a dose of 1200 mg/m2 and IFOS at a dose of 5 g/m2. Both drugs were administered i.v. over 24 hours on day one every three weeks. Adequate pre- and post hydration as well as use of Mesna in the Ifosfamide arm were mandatory. RESULTS: A median of two treatment cycles (range 1-12) per patient were given. In the chemotherapy-naive patients, in the CYCLO arm two PRs (RR 14%, C.I. 2-43%) were seen and in the IFOS arm two CRs, two PRs, (RR 25%, C.I. 7-52%) were observed. No responses were seen in pre-treated patients. The duration of responses were: 15+, 7+ months for the CRs, 15+ and 5 months for PRs in IFOS arm and 67+, 4 months in CYCLO arm. The hematological toxicity was dose-limiting and similar in both treatment arms. No serious non hematological toxicities were reported, but a transient increase of the creatinine blood level was seen in two IFOS patients (6%). CONCLUSION: Ifosfamide is an active drug in the treatment of chemotherapy-naive patients with advanced endometrial cancer and its application in currently used (combination) regimens should be considered.

Adenocarcinoma↗
PubMed1999

Adverse birth outcomes among native-born and immigrant women: replicating national evidence regarding Mexicans at the local level.

OBJECTIVES: For almost two decades, the literature has consistently described an epidemiologic paradox relating to better birth outcomes among high-risk groups, particularly new immigrants from Mexico and Southeast Asia. We hypothesize that regardless of their sociodemographic profile, Mexican immigrants will exhibit lower rates of low birth weight and preterm deliveries than native-(U.S.) born women of Mexican origin, non-Hispanic White and Black women, and Puerto Rican Women. METHODS: We studied 57,324 live-born singleton infants born to residents in the city of Chicago in a linked data set of 1994 birth-death records. Multivariate logistic regression was used to analyze race/ethnicity differentials in two pregnancy outcome measures, low birth weight and preterm birth. RESULTS: Overall better birth outcome is related to maternal immigrant status regardless of race/ethnic groups. Immigrant Mexican women had a significantly lower risk of both low birth weight [adjusted odds ratio (AOR): 0.78, 95% confidence interval (CI) 0.66-0.91] and preterm births (AOR: 0.75, 95% CI 0.65-0.86) and were at 28% and 33% lower risks of delivering a low birth weight infant or a premature infant, respectively, than non-Hispanic White women.

Adolescent↗
PubMed1999

UFT plus or minus calcium folinate for metastatic colorectal cancer in older patients.

Two studies were carried out to determine the activity and evaluate the toxicity of oral chemotherapy with uracil and tegafur in a 4:1 molar ratio (UFT) plus or minus calcium folinate in elderly patients with advanced colorectal cancer. In one study, 106 patients received a fixed dose of UFT 400 mg/day in two daily doses every 12 hours continuously, plus calcium folinate 45 mg/day administered in three divided doses every 8 hours continuously. In study 2, calcium folinate was omitted, and the dose of UFT was increased to 400 mg/m2/day in two daily doses administered every 12 hours continuously to 95 patients. Treatments for both studies were administered until grade 3 or grade 4 toxicity occurred or disease progressed. The response rate among the 96 available patients in study 1 was 17.7% (95% confidence interval [CI], 10% to 27%); 41 patients (43%) achieved an objective response or stable disease. Overall survival was 13.7 months with a statistically significant difference between patients with no progressive disease and patients with progressive disease (P < .01). In study 2, 62 of 95 patients have now been evaluated for response. The response rate was 21% (95% CI, 13% to 30%); 38 patients (61%) experienced an objective response or stable disease. The overall survival for study 2 has not yet been evaluated. Toxicity was generally mild, consisting of grade 3 nausea/vomiting (6% in study 1 and 2% in study 2), grade 3 or grade 4 diarrhea (11% in study 1 and 7% in study 2), plus one case of grade 3 mucositis in study 1. These findings suggest that chemotherapy with UFT (with or without modulation with calcium folinate) is feasible for elderly patients with advanced colorectal carcinoma.

Adenocarcinoma↗
PubMed1998

Frequency of Y chromosomal material in Mexican patients with Ullrich-Turner syndrome.

Cytogenetic studies have shown that 40-60% of patients with Ullrich-Turner syndrome (UTS) are 45,X, whereas the rest have structural aberrations of the X chromosome or mosaicism with a second cell line containing a structurally normal or abnormal X or Y chromosome. However, molecular analysis has demonstrated a higher proportion of mosaicism, and studies in different populations have shown an extremely variable frequency of Y mosaicism of 0-61%. We used Southern blot analysis and polymerase chain reaction (PCR) to detect the presence of Ycen, ZFY, SRY, and Yqh in 50 Mexican patients with UTS and different karyotypes to determine the origin of marker chromosomes and the presence of Y sequences. Our results indicated the origin of the marker chromosome in 1 patient and detected the presence of Y sequences in 4 45,X patients. Taken together, we found a 12% incidence of Y sequences in individuals with UTS. The amount of Y-derived material was variable, making the correlation between phenotype and molecular data difficult. Only 1 patient had a gonadoblastoma. We discuss the presence of Y chromosomes or Y sequences in patients with UTS and compare our frequency with that previously reported.

Adolescent↗
PubMed1998

Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with weekly high-dose 48-hour continuous-infusion fluorouracil for advanced colorectal cancer: a Spanish Cooperative Group for Gastrointestinal Tumor Therapy (TTD) study.

PURPOSE: The objective of this multicenter study was to compare the efficacy and toxicity profiles of a combination of 5-fluorouracil (5-FU) given by bolus injection together with intravenous leucovorin (LV) versus high-dose 5-FU in continuous infusion (CI) in the treatment of advanced colorectal cancer. PATIENTS AND METHODS: A total of 306 patients were randomized to receive either 5-FU 425 mg/m2 given by bolus injection on days 1-5 plus intravenous (i.v.) LV 20 mg/m2 every four to five weeks or 5-FU 3.5 g/m2/week in a 48-hour CI. Therapy was continued until disease progression. Second-line chemotherapy was allowed in both arms. RESULTS: The response rates in 306 patients with measurable lesions were 19.2% (modulated arm) and 30.3% (CI arm, P < 0.05). The median progression-free survival times were 23.5 weeks (modulated arm) and 25 weeks (CI arm, P = NS). Median survival times were 42.5 weeks (modulated arm) and 48 weeks (CI arm, P = NS). There were no significant differences in grade 3-4 toxicity profiles but if we consider all grades we observed more mucositis in the modulated arm and more hand-foot syndrome in the CI arm. CONCLUSIONS: In terms of response rate, the continuous infusion regimen was more effective than the modulated regimen. There was no significant difference in survival and time to progression, and none in grade 3-4 toxicity.

Adult↗
PubMed1998

Seventy-two hour epirubicin infusion plus quinidine in unresectable and metastatic adenocarcinoma of the pancreas: a phase II trial.

Twenty-two previously untreated patients who had unresectable and metastatic pancreatic cancer were treated in a prospective phase II trial with high-dose continuous infusion epirubicin (45 mg/m2 once every 24 hours continuous infusion days 4 through 6) plus quinidine (495 mg once every 24 hours on days 1-6). There were no objective responses (0 of 18 evaluable patients). Subjective responses were achieved in 2 of 21 evaluable patients (9%), all of whom had good performance status (Eastern Cooperative Oncology Group: 0-1). Median survival was 5.7 months for the overall population. Two patients who exhibited symptomatic improvement achieved responses lasting 7 and 13 months, respectively. Toxicity was generally mild and tolerable. Little benefit regarding survival and quality of life was observed with the use of this regimen. The role in chemoresistance of mdrl, p53, and the mismatch repair system was examined.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Evaluation of antiandrogen therapy in unresectable hepatocellular carcinoma: results of a European Organization for Research and Treatment of Cancer multicentric double-blind trial.

PURPOSE: The aim of the study was to evaluate the efficacy of antiandrogen therapy on overall survival and response in unresectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: A total of 244 patients with unresectable HCC were included in this multicentric double-blind trial. According to a two-by-two factorial design, patients were randomly assigned to receive one of the following treatments: pure antiandrogen plus placebo (A+P group, 60 patients); luteinizing hormone-releasing hormone (LHRH) agonist plus placebo (LHRH+P group, 62 patients); pure antiandrogen plus LHRH agonist (A+LHRH group, 62 patients); or placebo plus placebo (P+P group, 60 patients). Pure antiandrogen consisted of Anandron (Roussel-Uclaf Laboratory, Romainville, France) administered orally (300 mg daily for 1 month, then 150 mg daily). LHRH consisted of goseriline acetate (3.6 mg) or triptoreline (3.75 mg) administered monthly by subcutaneous injection. Treatment was given until death. Response was evaluated every 8 weeks according to World Health Organization (WHO) criteria. RESULTS: Six patients were considered ineligible. One patient had a complete response (A+P arm) and three had a partial response (two in the LHRH+P arm and one in the A+LHRH arm). An overall log-rank test did not demonstrate any significant difference in survival among the four arms. Taking the factorial design into account, comparison of survival showed no significant difference between Anandron-containing regimens and others, or between LHRH-containing regimens and others. No serious side effects occurred for any regimen. CONCLUSION: This controlled study shows clearly the lack of efficacy of androgen treatment in unresectable HCC.

Androgen Antagonists↗
PubMed1997

Dose-escalated paclitaxel in 1-hour infusion with a fixed dose of cisplatin in previously untreated advanced ovarian cancer: a phase II trial of the Spanish Group for Ovarian Cancer.

This phase II trial was planned to study the efficacy and toxicity of a fixed dose of cisplatin plus paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given over 1 hour with intrapatient dose escalation. Patients with advanced epithelial ovarian cancer (stages IIB-IV); Eastern Cooperative Oncology Group performance status < or = 2; normal renal, liver, and bone marrow function; and evaluable residual disease after debulking surgery were accrued. Paclitaxel was given over 1-hour infusion and dose was escalated from 175 to 200 and 225 mg/m2 if nadir neutrophil counts were > or = 1000/microL, platelets were > or = 100,000/microL, and neurotoxicity was less than grade 2. Cisplatin was given after paclitaxel at a fixed dose of 80 mg/m2. Six courses at 3-week intervals were planned. From May 1995 to August 1996, 68 patients were entered. Paclitaxel could not be escalated in six patients, another six received up to 200 mg/m2, and 45 received 225 mg/m2. Three hundred seventy-five courses were given: 27.7% at 175 mg/m2, 19.2% at 200 mg/m2, and 53.1% at 225 mg/m2. All patients were evaluable for toxicity, and 67 were evaluable for response. Thirty-five patients had a complete clinical response (51.4%), 20 had a partial response (29.4%), six had stable disease (8.9%), and six progressed on therapy (8.9%). Overall response rate was 80.8 (95% confidence interval, 71.3% to 90.1%). Second-look laparotomy was performed in 32 patients, and 20 of them (62.5%) had a pathologic complete remission. Grade 3 or 4 neutropenia was seen in 26 patients (38%), but only one had fever. Severe thrombocytopenia was not seen. Peripheral neurotoxicity (grade 1, 39.7%; grade 2, 42.6%; and grade 3, 8.8%) was dose-limiting. It is too early to report on time to progression and survival, and these data are not yet available. This combination of cisplatin with escalating doses of paclitaxel is feasible and very active, but the high incidence of peripheral neurotoxicity may limit its use.

Antineoplastic Agents↗
PubMed1997

"H" reflex as a measure of subclinical uremic polyneuropathy in children with chronic renal failure.

Uremic polyneuropathy (UPNP) is a serious complication of chronic renal failure (CRF) in adults; however, its prevalence is unknown in the pediatric population. An easy-to-perform maneuver for its detection in children is the evaluation of "H" reflex. The objective of this study was to validate the usefulness of the "H" reflex maneuver for the diagnosis of UPNP in pediatric dialysis patients for CRF. Thirty-seven CRF patients were paired with healthy controls by age and sex. The patients were being treated with dialysis or one of its variants. Information was obtained regarding diagnosis, duration, and control of dialysis. Neurological examination was performed, conduction velocities in sensory and motor nerves were measured, and "H" reflex elicited bilaterally. Peripheral polyneuropathy was determined by the presence of at least two nerves with alterations in latency and/or conduction velocities. It was found that 59.4% (22/37) of the children with CRF treated with dialysis developed UPNP, 17 with ambulatory peritoneal dialysis, and 5 with hemodialysis. There was no difference in diagnosis, duration of dialysis, or control of the same in these patients from other CRF patients who did not have UPNP. All patients were clinically asymptomatic. "H" reflex showed a sensibility of 44%, a specificity of 87%, a predictive value positive of 66%, and a predictive value negative of 76%, when measured to 28 msec. With a 30 msec duration specificity rises to 95%. UPNP presents asymptomatically in pediatric patients. "H" reflex is an adequate screening test for the selection of pediatric patients to be tested further.

Adolescent↗
PubMed1996

Molecular analysis in true hermaphrodites with different karyotypes and similar phenotypes.

True hermaphroditism is characterized by the development of ovarian and testicular tissue in the same individual. Müllerian and Wolffian structures are usually present, and external genitalia are often ambiguous. The most frequent karyotype in these patients is 46,XX or various forms of mosaicism, whereas 46,XX is very rarely found. The phenotype in all these subjects is similar. We studied 10 true hermaphrodites. Six of them had a 46,XX chromosomal complement: 3 had been reared as males and 3 as females. The other 4 patients were mosaics: 3 were 46,XX/46,XY and one had a 46,XX/47,XXY karyotype. One of the 46,XX/46,XY mosaics was reared as a female, whereas the other 3 mosaics were reared as males. The sex of assignment in the 10 patients depended only on labio-scrotal differentiation. Molecular studies in 46,XX subjects documented the absence of Y centromeric sequences in all cases, arguing against hidden mosaicism. One patient presented Yp sequences (ZFY+, SRY+), which contrast with South African black 46,XX true hermaphrodites in whom no Y sequences were found. Molecular analysis in the subjects with mosaicism demonstrated the presence of Y centromeric and Yp sequences confirming the presence of a Y chromosome. Gonadal development, endocrine function, and phenotype in the 10 patients did not correlate with the presence of a Y chromosome or Y-derived sequences in the genome, confirming that true hermaphroditism is a heterogeneous condition.

Adolescent↗
PubMed1996

Outpatient weekly high-dose continuous-infusion 5-fluorouracil plus oral leucovorin in advanced colorectal cancer. A phase II trial. Spanish Cooperative Group for Gastrointestinal Tumor Therapy (TTD).

BACKGROUND: In a previous phase I-II trial we showed that the maximum tolerable dose (MTD) of 5-fluorouracil (5-FU) in a weekly 48-hour continuous infusion (CI) was 3.5 g/m2. In a subsequent confirmative phase II trial with 85 evaluable patients, a 38.5% response rate was obtained, and a median survival of 12 months. These data were comparable to those achieved by biochemical modulation of 5-FU with leucovorin. On this basis we attempted to modulate high-dose 5-FU (3 g/m2) with oral leucovorin (LV) but the regimen was too toxic and the dose had to be reduced. A new phase II trial with 2 g/m2/week plus oral leucovorin was planned. PATIENTS AND METHODS: From July 1992 to June 1994, 110 previously untreated patients with advanced, measurable colorectal cancer were included in a multicenter study. The patients received, on an outpatient basis, 5-FU 2 g/m2 by continuous infusion for 48 hours once a week until progression or the appearance of toxic effects. Oral leucovorin (60 mg every six hours) was also given during the 5-FU infusion. RESULTS: Patients received a median dose intensity of 5-FU of 1.6 g/m2/week (range 0.9-2). Three complete responses and 36 partial responses were observed. The overall response rate was 37.5% (95% CI, 28% to 46.8%), the median time to progression 7.4 months and median survival 14.5 months. W.H.O. grade 3 diarrhea occurred in 27 patients (24.5%); grade 3 mucositis was observed in 9 (8.1%) patients and grade 4 in one. Grade 3 nausea and vomiting was reported in 13 (11.7%) patients, while grade 3 hand-foot syndrome was detected in only 5 (4.5%). Grade 4 leukopenia occurred in one patient and grade 3-4 thrombocytopenia in two. CONCLUSIONS: Oral leucovorin modulation of weekly 48-hour continuous infusion of 5-FU at 2 g/m2 is an active regimen, with diarrhea and mucositis as the main limiting toxic effects. Its antitumor activity does not seem superior to that obtained with a weekly 48-hour continuous infusion of 5-FU alone at a dose of 3.5 g/m2.

Administration, Oral↗