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A Carrato,
A Gómez,
P Escudero,
M Chaves,
F Rivera,
E Marcuello,
E González,
C Grávalos,
M Constenla,
J Luis Manzano,
F Losa,
J Maurel,
R Dueñas,
B Massuti,
J Gallego,
J Aparicio, A Antón,
E Aranda
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ABSTRACT: PURPOSE: To evaluate the efficacy and safety profile of the combination of panitumumab and irinotecan every 3 weeks in a phase II trial as second-line treatment in patients with advanced wild-type (WT) K-RAS colorectal cancer (CRC). METHODS: Fifty-three patients received 9 mg/kg of panitumumab followed by 350 mg/m(2) of irinotecan every 21 days until disease progression, unacceptable toxicity or consent withdrawal. RESULTS: Median age of patients included was 67 years. All patients had previously received 5-fluorouracil, 84 % oxaliplatin and 8 % irinotecan as first-line treatment. Patients received a median of five infusions of panitumumab and irinotecan. On an intention-to-treat analysis, 12 patients (23 %) achieved partial responses and 22 patients (41 %) achieved disease stabilization. Median progression-free survival and overall survival were 4.5 and 15.1 months, respectively. The most frequent treatment-related severe toxicities per patient were diarrhoea (35.8 %), followed by skin rash (32.1 %), asthenia (18.9 %) and neutropenia (13.2 %). A significant association between clinical response and incidence and grade of skin toxicity was observed (p = 0.0032). CONCLUSION: This study shows that the administration of panitumumab plus irinotecan every 3 weeks is safe, active and feasible as second-line treatment in patients with advanced WT K-RAS CRC.
Clinical and Translational Oncology 01/2013; · 1.33 Impact Factor
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A Antón,
J Montalar,
J Carulla,
C Jara,
N Batista,
C Camps,
J Cassinello,
J Sanz-Ortiz,
E Díaz-Rubio,
C Martínez,
F Ledesma,
E Zubillaga
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ABSTRACT: Despite effective analgesic therapy, inadequate pain control is frequently perceived by patients and caregivers.
To assess satisfaction with management of pain in cancer patients.
Between January and May 2007, a cross-sectional multicentre study was conducted in 64 Medical Oncology Departments throughout Spain. A total of 525 outpatients with oncological diseases completed a questionnaire with demographic data, characteristics and intensity of pain, and perceptions and attitudes towards pain management at the time of a routine clinical visit. Physicians also completed a questionnaire with tumour-related and treatment-related data. Cluster analysis was used to classify patients into three groups (satisfied, neither satisfied nor dissatisfied or neutral, dissatisfied) according to pain intensity and satisfaction with treatment.
Patients satisfied with their analgesic treatment (33%) had lower pain intensities and, when regularly asked about their pain, considered their physicians to be more involved in their treatment. Neither satisfied nor dissatisfied patients (neutral) (44%) had higher mean pain intensities. Two-thirds of them achieved marked relief of their pain and also thought that physicians were aware of their situation. Dissatisfied patients (23%) had moderate to severe pain intensities, and said that they were asked less frequently about their pain, and thought that their physicians were less involved in their analgesic treatment.
Physician-patient communication and information provided to patients are essential aspects of patient perceptions and attitudes towards control of cancer-related pain. Pain is seen as a condition that may be controlled but affects the capacity to lead a normal life.
European journal of pain (London, England) 12/2011; 16(3):381-9. · 3.37 Impact Factor
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A Antón,
A Ruiz,
A Plazaola,
L Calvo,
M A Seguí,
A Santaballa,
M Muñoz,
P Sánchez,
A Miguel,
E Carrasco,
J Lao,
J Camps,
J Alfaro,
S Antolín,
M C Cámara
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ABSTRACT: we previously reported a phase I trial of liposome-encapsulated doxorubicin citrate (LD), docetaxel and trastuzumab as neoadjuvant in stages II and IIIA human epidermal growth factor receptor 2-overexpressing breast cancer patients. This study evaluates the efficacy of this regimen in a phase II trial.
patients were treated with LD 50 mg/m(2) and docetaxel 60 mg/m(2) every 21days associated with standard trastuzumab dose and pegfilgrastim support.
fifty-nine patients were enrolled; median age: 48 years (range 24-71 years); premenopausal patients: 36 (61%); 19 patients (32%) presented stage IIIA disease and 40 patients (67%) stage II; histological grades 2-3 tumors: 50 patients (84%) and estrogen receptor-progesterone receptor negative: 28 patients (47%). In all, 27% achieved a pathological complete response in breast and axilla (grade 5-Miller and Payne classification); 15% of patients achieved grade 4. Clinical and radiological response rates were 86% and 81%, respectively. Forty-two patients (71%) underwent breast-conserving surgery. The main grades 3-4 toxic effects were non-febrile neutropenia (29%) and fatigue (8%). Grade 2 left ventricular ejection fraction decline was observed in nine patients. No congestive heart failure was observed.
LD plus docetaxel combination associated with trastuzumab as neoadjuvant is active in breast cancer and entails a favorable cardiotoxicity profile. This regimen is a new treatment option in these patients.
Annals of Oncology 01/2011; 22(1):74-9. · 6.43 Impact Factor
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ABSTRACT: A cohort of 35 patients with advanced colorectal cancer, not previously exposed to chemotherapy, were included in a phase II study exploring the combination ofinterferon-alpha, 9 MU subcutaneously three times weekly, and 5-fluorouracil 750 mg/nf/day during 5 consecutive days in continuous intravenous infusion followed with weekly bolus injection offluorouracil 750mg/m2. Of 33 cases evaluablefor activity; 5 patients achieved partial response and 3 complete response for an overall response rate of 24% (95%; confidence limit 11-42 %). Most of the responses were observed in liver metastases, response rate = 30% (95%; CL 13-53%), with little activity observed in other sites; response rate 3% (95%; CL 8-16%), p =. 0006. The median time to progression and median overall survival were 16+ (range 1+ to 48+) and 21+ weeks (range 1+ to 52+). All patients were evaluablefor analysis of toxicity. Severe mucositis and diarrhea, present in 14 patients were the limiting side effects. Two patients developed progressive renal toxicity and died. Weakness, myalgia, and nonneutropenic fever were observed frequently, one patient developed dementia. This combination is able to induce major responses in patients with advanced colorectal cancer, particularly in liver metastasis. Additional trials evaluating this approach are indicated.
06/2009; 10(4):259-264.
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ABSTRACT: We carried out a phase I clinical trial to establish the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of the combination of liposome-encapsulated doxorubicin citrate (LD) and docetaxel in breast cancer patients.
Patients with HER-2-overexpressing stages II and IIIA breast cancers were treated in different dose cohorts of three patients. The MTD cohort was expanded up to six patients. The patients received LD and docetaxel every 21 days, plus weekly trastuzumab, with pegfilgrastim support.
A total of 20 patients were enrolled, 18 of them being assessable for toxicity and response. DLTs observed for this combination were diarrhea, fatigue, febrile neutropenia, stomatitis, myalgia, and nonneutropenic infection (pneumonia). LD 50 mg/m(2) and docetaxel 60 mg/m(2) every 21 days have been the MTD, with no episode of DLT observed. Seven patients developed left ventricular ejection fraction decline (six grade 1 and one grade 2). No interruptions of the treatment were needed as a consequence of cardiac toxicity. Pathologic complete response was achieved in eight patients (44%).
The MTD and recommended dose for phase II trials of LD and docetaxel are 50 and 60 mg/m(2), respectively. The achieved results on cardiotoxicity are promising.
Annals of Oncology 01/2009; 20(3):454-9. · 6.43 Impact Factor
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ABSTRACT: The "Alamo" project is a retrospective analysis of 14,854 patients diagnosed of breast cancer between 1990 and 1997 in 50 Spanish hospitals.
Alamo I (AI) consisted of 4,532 patients diagnosed with breast cancer between 1990 and 1993. Data were collected in 2000. Alamo II (AII) consisted of 10,322 patients diagnosed between 1994 and 1997. Data were collected in 2003.
At presentation, there were (AI vs. AII) 17.6% vs. 24.3% at stage I; 55.5% vs. 53.1% at stage II; 18.7% vs. 15% at stage III; 7.2% vs. 5.9 at stage IV. Median age was 57 (AI) vs. 58 years (AII) and 65.9% vs. 67.2% (AI vs. AII) were post-menopausal. Firstline treatment for disease stages I, II and III was surgery in 91% of patients in both studies. Breast conserving surgery rate increased from 20.2% (AI) to 32.7% (AII). Adjuvant systemic treatments were administered to 87.6% (AI) and 92.8% (AII) of patients. Recurrence rate diminished from 36.6% (AI) to 22.5% (AII) and the 9-year survival rate increased from 63.2% (95% CI: 61.5-64.9) to 70.1% (95% CI: 68.5-71.8).
Breast cancer outcomes in Spain have improved from 1990-1993 to 1994-1997, likely because of breast cancer screening program implementation and new therapies.
Clinical and Translational Oncology 08/2006; 8(7):508-18. · 1.33 Impact Factor
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M Martín,
A Lluch,
M A Seguí,
A Ruiz,
M Ramos,
E Adrover,
A Rodríguez-Lescure,
R Grosse,
L Calvo,
C Fernandez-Chacón,
M Roset, A Antón,
D Isla,
P Martínez del Prado,
L Iglesias,
J Zaluski,
A Arcusa,
J M López-Vega,
M Muñoz,
J R Mel
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ABSTRACT: The aim of the study was to analyse the toxicity and health related quality of life (HRQoL) of breast cancer patients treated with FAC (5-fluorouracil, doxorubicin, cyclophosphamide) and TAC (docetaxel, doxorubicin, cyclophosphamide) with and without primary prophylactic G-CSF (PPG).
This was a phase III study to compare FAC and TAC as adjuvant treatment of high-risk node-negative breast cancer patients. After the entry of the first 237 patients, the protocol was amended to include PPG in the TAC arm due to the high incidence of febrile neutropenia. A total of 1047 evaluable patients from 49 centres in Spain, two in Poland and four in Germany were included in the trial. Side-effects and the scores of the EORTC QLQ-C30 and QLQ BR-23 questionnaires were compared in the three groups (FAC, TAC pre-amendment and TAC post-amendment).
The addition of PPG to TAC significantly reduced the incidence of neutropenic fever, grade 2-4 anaemia, asthenia, anorexia, nail disorders, stomatitis, myalgia and dysgeusia. Patient QoL decreased during chemotherapy, more with TAC than FAC, but returned to baseline values afterwards. The addition of PPG to TAC significantly reduced the percentage of patients with clinically relevant Global Health Status deterioration (10 or more points over baseline value) at the end of chemotherapy (64% versus 46%, P<0.03).
The addition of PPG significantly reduces the incidence of neutropenic fever associated with TAC chemotherapy as well as that of some TAC-induced haematological and extrahaematological side-effects. The HRQoL of patients treated with TAC is worse than that of those treated with FAC but improves with the addition of PPG, particularly in the final part of chemotherapy treatment.
Annals of Oncology 08/2006; 17(8):1205-12. · 6.43 Impact Factor
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A Antón,
E Aranda,
A Carrato,
E Marcuello,
B Massutti,
A Cervantes,
A Abad,
J Sastre,
C Fenández-Martos,
M Gallén,
E Díaz-Rubio,
L Huarte,
M Balcells
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ABSTRACT: The efficacy and toxicity of irinotecan (CPT-11) 350 mg/m(2) i.v. once every 3 weeks was assessed in 60 patients with advanced colorectal cancer (CRC) showing failure to 5-fluorouracil (5-FU) treatment. The overall objective response rate was 13.6% (1 complete response and 4 partial responses) and 25 patients (42.4%) showed stable disease; the median time to disease progression was 4.4 months and the median survival was 10.5 months. The main non-hematological toxicities were alopecia (80.3% of patients), diarrhea (75.0%), and nausea/vomiting (71.7%); neutropenia was the main hematological toxicity. Grade 3 or 4 diarrhea appeared in 21 of 131 cycles (16.1%), whereas grade 3 or 4 neutropenia appeared in 78 cycles (25.0%). In conclusion, the present phase II study confirms that CPT-11 350 mg/m(2) every 3 weeks is active and well tolerated as second-line chemotherapy for CRC in 5-FU resistant patients.
Methods and Findings in Experimental and Clinical Pharmacology 11/2003; 25(8):639-43. · 0.93 Impact Factor
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ABSTRACT: To evaluate the efficacy and the toxicity profile of the sequential administration of doxorubicin and docetaxel as first-line chemotherapy in metastatic breast cancer (MBC).
Eighty-one patients received a total of 436 cycles of chemotherapy: 236 of doxorubicin (75 mg/m2) and 200 of docetaxel (100 mg/m2 every 21 days). The first 35 patients received doxorubicin every 14 days with G-CSF support, and in the other 46 cases doxorubicin was administered every 21 days without G-CSF.
After entire treatment the overall response rate was 65% (18 complete responses). With a median follow-up of 19 months (range, 1-48 months), the median time to progression was 11.3 months and the median survival time was 31 months. As expected, febrile neutropenia was the most important toxicity and it appeared in 26 cycles (6%) and 19 patients (23%). In the patients that received doxorubicin every 14 days, the febrile neutropenia incidence was higher during docetaxel treatment, especially after its first administration.
The dose and schedule of doxorubicin and docetaxel used in this trial seems to be active in first-line treatment of patients with MBC. The toxicity profile appears to be better than observed with concomitant schedules.
Breast Cancer Research and Treatment 02/2003; 77(1):1-8. · 4.43 Impact Factor
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ABSTRACT: The aim of this study was to determine the maximum-tolerated dose (MTD) and dose-limiting toxicity (DLT) of weekly Irinotecan (CPT-11) plus UFT, and to assess the antitumour activity of this combination as second-line chemotherapy in patients with advanced colorectal carcinoma, 31 patients with measurable advanced colorectal carcinoma were treated. Cohorts of 3 patients received increasing dose levels of the combination. Levels 1 to 4 included a fixed dose of oral (p.o.) UFT (250 mg/m(2)/day) for 21 days of a 28-day cycle combined with increasing intravenous (i.v.) doses of CPT-11 (80, 100, 110 and 120 mg/m(2)) on days 1, 8 and 15. Levels 5 and 6 included a higher fixed dose of oral UFT (300 mg/m(2)) combined with increasing i.v. doses of CPT-11 (100 and 110 mg/m(2)) on days 1, 8 and 15. 147 courses were administered. MTD were reached at level 4 (2 cases of grade 4 diarrhoea and 1 grade 3 asthenia), and level 6 (1 grade 4 diarrhoea, 1 grade 3 diarrhoea and 1 grade 3 febrile neutropenia). Responses in 30 evaluable patients were: 3 partial responses (10%), 15 stable disease (50%) and progressive disease in 12 patients (40%). Median time to progression was 4.5 months (95% Confidence Interval (CI): 3.4-6.6 months) and median survival was 11 months (95% CI: 7.9-14.1 months). The recommended doses for phase II trials are: (a) CPT-11 110 mg/m(2) i.v. on days 1, 8 and 15 every 28 days plus UFT 250 mg/m(2) p.o. on days 1 through to 21 or (b) CPT-11 100 mg/m(2) and UFT 300 mg/m(2).
European Journal of Cancer 01/2002; 37(18):2385-91. · 5.54 Impact Factor
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ABSTRACT: Gemcitabine (2',2'-difluorodeoxycytidine) is a nucleoside analog with antitumor activity against a variety of malignancies. The critical enzyme cytidine kinase is saturated at plasma concentrations achieved after a 30-min infusion at conventional doses. Prolonged infusion time may yield higher intracellular dFdCTP concentrations. A phase I study was designed to determine the maximum tolerated dose (MTD) of gemcitabine, given by infusion for 3 h, in heavily pretreated patients. Twenty-seven patients (13 head and neck cancer, seven sarcoma, three esophageal cancer, three non-small-cell lung cancer and one ovarian cancer) were enrolled. Twenty patients were defined as refractory at first- or second-line chemotherapy. Four different entry dose levels (300, 400, 450 and 500 mg/m(2)) were evaluated for gemcitabine administered on days 1, 8 and 15 of a 28-day cycle. The MTD was defined as 450 mg/m(2), with granulocytopenia, thrombocytopenia and asthenia being dose limiting. The maximum grade III/IV patient toxicities for hemoglobin, leukocytes, neutrophils and platelets for all doses were 7, 19, 19 and 11%, respectively. Non-hematological toxicities included asthenia, nausea/vomiting and diarrhea. Thus, gemcitabine administered at a fixed 3-h infusion was well tolerated up to 450 mg/m(2) in heavily pretreated patients. Myelosupression and asthenia were dose-limiting toxicities.
Anti-Cancer Drugs 11/2001; 12(9):713-7. · 2.41 Impact Factor
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ABSTRACT: A group of 70 patients with locally advanced non-small-cell lung cancer (LA-NSCLC), treated in different phase II-III trials with platinum-based chemotherapy in two institutions, have been evaluated to identify potential baseline prognostic factors predicting their survival. The eligibility criteria were patients with stage IIIA (N2)-IIIB, Eastern Cooperative Oncology Group performance status 0.1 and less than 5% weight loss. All 37 patients with stage IIIA(N2) were treated with platinum-based induction chemotherapy followed by surgery plus radiotherapy if no progression was observed. The other 33 patients with stage IIIB were treated with platinum-based induction chemotherapy followed by conventional fractionation radiotherapy if no progression was observed. The overall response rate to induction chemotherapy was 40%. Median survival of the 70 patients was 13 months, with a 4-year survival of 15%. At univariate analysis, two prognostic factors correlated with survival: partial or complete response to induction chemotherapy (P<0.00001) and bulky mediastinal lymph nodes (N2>2.5 cm) (P=0.03). At multivariate analysis, only the response to induction chemotherapy retained statistical significance (P=0.00001). Randomized well-balanced prospective trials considering initially mediastinal N2 node size are needed to clearly establish the role of chemotherapy, surgery and radiotherapy in LA-NSCLC.
Lung Cancer 11/2000; 30(2):107-16. · 3.43 Impact Factor
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ABSTRACT: Information on the relative cost-effectiveness of treatments for cancer is being increasingly sought as pressure on health care resources increases. The objective of this study was to assess the cost-effectiveness of gemcitabine/cisplatin (GC) versus cisplatin/etoposide (CE) in patients with advanced non-small cell lung cancer (NSCLC), using resource utilization data collected in conjunction with the first randomized clinical trial comparing both combinations.
Efficacy and medical care resource utilization data were collected prospectively in an open-label, multicenter, randomized, comparative, phase III trial conducted in Spain which compared gemcitabine/cisplatin and cisplatin/etoposide in 135 chemonaive patients with Stage IIIB or IV NSCLC. There were no differences between both regimens when survival was used as primary end-point, so a cost-minimization analysis was used to compare them. In addition, cost-effectiveness analyses were conducted when percentage of responses and time to progression were used as secondary end-points.
There were no differences between both regimens when survival was selected as the efficacy end-point. Despite the higher chemotherapy cost of GC when compared to CE, there were no differences in total direct costs (584523 pts for GC and 589630 pts for CE; P=NS) between both regimens. Potential savings with GC were mainly associated with a decrease in hospitalization rate. There were differences in favor of GC when response rate (40.6% for GC and 21.9% for CE; P<0.05) and time to disease progression (8.7 months for GC and 7.2 months for CE; P<0. 05) were used as clinical end-points. GC presented a favorable cost-effectiveness profile when compared to CE.
This prospective economic evaluation conducted alongside a clinical trial offers valuable preliminary information on the potential efficiency of the combination gemcitabine-cisplatin in NSCLC. Future assessments based on larger clinical trials focused on survival and naturalistic economic studies conducted in real clinical practice settings are necessary to confirm these findings.
Lung Cancer 05/2000; 28(2):97-107. · 3.43 Impact Factor
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E Díáz-Rubio,
J Sastre,
A Abad,
M Navarro,
E Aranda,
A Carrato,
M Gallén,
E Marcuello,
J Rifá,
T Massuti,
A Cervantes, A Antón,
C Fernández Martos
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ABSTRACT: 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.
Oncology (Williston Park, N.Y.) 08/1999; 13(7 Suppl 3):35-40. · 1.03 Impact Factor
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F Cardenal,
M P López-Cabrerizo, A Antón,
V Alberola,
B Massuti,
A Carrato,
I Barneto,
M Lomas,
M García,
P Lianes,
J Montalar,
C Vadell,
J L González-Larriba,
B Nguyen,
A Artal,
R Rosell
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ABSTRACT: We conducted a randomized trial to compare gemcitabine-cisplatin with etoposide-cisplatin in the treatment of patients with advanced non-small-cell lung cancer (NSCLC). The primary end point of the comparison was response rate.
A total of 135 chemotherapy-naive patients with advanced NSCLC were randomized to receive either gemcitabine 1,250 mg/m2 intravenously (IV) days 1 and 8 or etoposide 100 mg/m2 IV days 1 to 3 along with cisplatin 100 mg/m2 IV day 1. Both treatments were administered in 21-day cycles. One hundred thirty-three patients were included in the intent-to-treat analysis of response.
The response rate (externally validated) for patients given gemcitabine-cisplatin was superior to that for patients given etoposide-cisplatin (40.6% v 21.9%; P = .02). This superior response rate was associated with a significant delay in time to disease progression (6.9 months v 4.3 months; P = .01) without an impairment in quality of life (QOL). There was no statistically significant difference in survival time between both arms (8.7 months for gemcitabine-cisplatin v 7.2 months for etoposide-cisplatin; P = .18). The overall toxicity profile for both combinations of drugs was similar. Nausea and vomiting were reported more frequently in the gemcitabine arm than in the etoposide arm. However, the difference was not significant. Gemcitabine-cisplatin produced less grade 3 alopecia (13% v 51%) and less grade 4 neutropenia (28% v 56% ) but more grade 3 and 4 thrombocytopenia (56% v 13%) than did etoposide-cisplatin. However, there were no thrombocytopenia-related complications in the gemcitabine arm.
Compared with etoposide-cisplatin, gemcitabine-cisplatin provides a significantly higher response rate and a delay in disease progression without impairing QOL in patients with advanced NSCLC.
Journal of Clinical Oncology 02/1999; 17(1):12-8. · 18.37 Impact Factor
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ABSTRACT: There is need for more active and better tolerated combinations in non-small cell lung cancer (NSCLC). The Spanish Lung Cancer Group (SLCG) therefore conducted this phase II study to define the efficacy and toxicity profile of the combination of higher doses than usual of gemcitabine along with cisplatin in patients with advanced NSCLC.
Forty patients with pathologically documented advanced NSCLC were included in this trial (34 men, six women; aged 34-74 years; mean 64 years). Twenty-two patients had unresectable stage IIIB disease and 18 had stage IV disease. Karnofsky performance status was > or =70%. In five patients, surgery had previously been performed and four patients had received radiotherapy. Gemcitabine at a dose of 1200 mg/m2 was administered weekly (days 1, 8 and 15) and cisplatin 100 mg/m2 on day 15 of each 28-day cycle.
Responses were scored according to standard World Health Organization criteria. Of 40 assessable patients, 19 had a partial response for an overall response rate of 47.5% (95% confidence interval (CI) 32-64%). To date, median survival for the whole group is 10.4 months (95% CI 6.2-11.7 months), with a 1-year survival rate of 35%. Toxicity was mainly haematological. Seven patients (18%) had grade 4 neutropenia (one episode of febrile neutropenia). Thrombocytopenia (12.8% grade 3 and 2.6% grade 4) was not associated with clinical bleeding. One patient had a grade 4 transient rise in transaminase. There was no grade 3 or 4 renal toxicity. There was no grade 4 symptomatic toxicity. The most common grade 3 toxicities were nausea and vomiting (28.2%) and alopecia (10.3%) both related to cisplatin.
Gemcitabine can be safely administered at a dose of 1200 mg/m2 in combination with cisplatin. Thrombocytopenia seems to be less than in schedules with cisplatin given on day 1. The results of this studyshow promising activity (47.5% response rate) with modest toxicity. As this combination of gemcitabine and cisplatin deserves further evaluation in prospective randomized trials, the SLCG is comparing gemcitabine-cisplatin with etoposide-cisplatin in a phase III randomized study.
Lung Cancer 12/1998; 22(2):139-48. · 3.43 Impact Factor
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A Abad,
B Massuti,
E Blanco,
A Carrato,
J Maurel,
A Cervantes,
E Aranda, A Antón,
J M Vicent,
J Dorta,
M L Garcia de Paredes,
A Ariza
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ABSTRACT: 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.
American Journal of Clinical Oncology 04/1998; 21(2):151-4. · 2.01 Impact Factor
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ABSTRACT: After a 26% response rate was reported with a 20/mg/m2/week vinorelbine (VRL) dose, a multicenter phase II trial of a modified weekly VRL treatment protocol (30 mg/m2 days 1 and 8 every 21 days) for unresectable non-small cell lung cancer (NSCLC) was designed to determine its clinical activity, toxicity, and survival of treated patients. As myelotoxicity frequently precludes the administration of VRL, by suppressing the dose that would correspond to day 15 of a weekly protocol, we allowed bone marrow recovery to take place and avoided the administration of the drug at the nadir of the cycle. The trial included 71 consecutive, previously untreated patients with unresectable and measurable disease. A total of 297 three-week treatment courses were administered with an average of 4 courses per patient (range 1-11). Results showed that in spite of attaining a median dose intensity of 19 mg/m2/week, this modified weekly VRL treatment regimen has a low level of activity (7.5% response rate) in NSCLC. Although a more tolerable level of toxicity is achieved, in order to maintain its antitumor activity, the recommended dose of VRL when given alone for NSCLC treatment (30 mg/m2/weekly) should not be decreased.
Lung Cancer 08/1997; 17(2-3):261-9. · 3.43 Impact Factor
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ABSTRACT: To evaluate a new anthracycline 4'-iodo-4'-deoxydoxorubicin (I-DOX) in patients with measurable advanced colorectal adenocarcinoma in a phase II study.
We investigated therapeutic activity and toxicities associated with repeated courses of I-DOX 80 mg/m2 administered every 3 weeks. Eighteen patients entered the trial, all of them evaluable for response and toxicity.
A total of 47 courses were administered. The median cumulative I-DOX dose was 238 mg/m2 (80-320). Myelosuppression, particularly leukopenia, was the most frequent and serious side effect associated with I-DOX treatment; World Health Organization (WHO) grade 3-4 leukopenia occurred in 4 patients (22%). No thrombocytopenia was observed except in 1 patient who presented WHO grade 4. Only 1 patient developed febrile neutropenia but recovered uneventfully. Overall, the I-DOX treatment was well tolerated. Grade 3-4 nausea/vomiting was observed in 2% of the cycles and no other severe toxicities were recorded. Echocardiography or multiple gated scan was performed before treatment and during follow-up in 14 patients to measure left ventricular ejection fraction (LVEF), and a decrease > 15% was detected in 3, including 1 whose LVEF fell below normal values (48%) (normal range > 49%). There were no cases of congestive heart failure or treatment-related deaths. No complete or partial response (PR) was observed. Twelve patients received weekly high-dose 5-fluorouracil (WFU) as rescue. Four patients had PR, 5 no change and 3 progressive disease (PD). The median time to PD of the whole group from study entry to failure after WFU was 30 weeks and the overall median survival was 11 months.
As reported for other anthracyclines, I-DOX showed no activity in colorectal adenocarcinoma; however, the use of an investigational agent as front-line chemotherapy for colorectal adenocarcinoma does not compromise further response to 5-FU.
Tumori 04/1994; 80(2):124-7. · 0.86 Impact Factor
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ABSTRACT: One hundred sixty consecutive patients with histologically confirmed colorectal cancer (advanced disease) without prior chemotherapy were entered in a randomized trial comparing 5-fluorouracil (5-FU) 1,000 mg/m2 intravenously per day for 5 consecutive days in continuous infusion versus cisplatin (CP) 100 mg/m2 on day 1 plus 5-FU as described on days 2 to 6. In both arms, treatment was recycled every 4 weeks. Both groups were well balanced for age, sex, colon or rectal origin, median time between diagnosis to advanced disease, performance status at entry, and visceral involvement. The overall response rate in the combination and in the single arm were 18 and 23%, respectively. There were no differences in time to progression (a median of 17.8 and 14.9 weeks for CP-5-FU and 5-FU, respectively) and in overall survival (a median of 71.2 and 59.6 weeks, respectively). The incidence of grade 3-4 emesis was significantly higher in the CP-containing chemotherapy (p = .00001). Our study has failed to demonstrate any clinical benefit from adding cisplatin to 5-FU in patients with cancer of the colon and rectum.
American Journal of Clinical Oncology 03/1992; 15(1):56-60. · 2.01 Impact Factor
