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1.
S. Cascinu Paolo Alessandroni David Rossi Elena Del Ferro Anna Fedeli Virginia Casadei Giuseppina Catalano 《Cancer chemotherapy and pharmacology》1996,38(4):385-386
A total of 26 patients with advanced colorectal cancer received 60 mg/m2 methotrexate i. v. on days 1 – 4; 400 mg/m2 5-fluorouracil i. v. on days 2, 3, 5, and 6; and 100 mg/m2 6S-leucovorin i. v. on days 2, 3, 5, and 6. Interferon-α2b at a dose of 3 million U was given i. m. daily for the 6 days
of chemotherapy. Courses were repeated every 3 weeks. There were four partial responses for a response rate of 15% (95% confidence
interval 2 – 28%). In all, 14 patients expressed grade 3 toxicity; 9 patients had diarrhea, 3 had stomatitis, and 2 developed
leukopenia. In conclusion, multimodal biochemical modulation of 5-fluorouracil, at least on this schedule, does not seem to
be effective, as it results in severe toxicity.
Received: 5 November 1995 / Accepted: 17 January 1996 相似文献
2.
A. Polyzos N. Tsavaris A. Giannopoulos C. Bacoyiannis V. Papadimas N. Kalahanis G. Karatzas C. Kosmas N. Sakelaropoulos A. Archimandritis A. Papachristodoulou P. Kosmidis 《Cancer chemotherapy and pharmacology》1996,38(3):292-297
Recent advances in biochemical pharmacology have revealed the basis for the biological modulation of 5-fluorouracil (5-FU)
by methotrexate (MTX) and folinic acid (FA). Sequential use of MTX given 24 h prior to 5-FU has resulted in enhanced cell
kill in vitro and in vivo. In addition, administration of FA prior to 5-FU has led to potentiation of 5-FU action by stabilization
of the ternary complex of thymidine synthase. In the present randomized study, two groups of patients with advanced colorectal
cancer were treated as follows: 43 patients (pts) in group A received 5-FU + FA, whereas 45 pts in group B received 5-FU +
FA + MTX. The dosage was as follows: group A received FA i. v. at 300 mg/m2 per day, prior to i. v. 5-FU at 500 mg/m2 per day on days 1 – 4; group B was given MTX i. v. at 130 mg/m2 per day on day 0, followed 24 h later by FA at 15 mg q6h × 6, and 5-FU + FA was started on day 1 and given at the same doses
and schedule described for group A. Objective responses were achieved by 8/43 pts in group A (1 complete response and 7 partial
responses) and by 18/45 pts in group B (3 complete and 15 partial responses), all occurring in the liver. There was no significant
difference in the median time to progression (group A 6.1 months, group B 6.8 months) or the median survival (group A 9.2
months, group B 10.3 months). Toxicity was significantly greater in group B [grade 2 – 3 mucositis 20% versus only 2% in group
A (P <0.0001); grade 3 diarrhea in group B 15% versus 3% in group A (P <0.001)]. According to our results, double biological modulation of 5-FU with MTX + FA led to an enhanced response rate with
increased toxicity as compared with the 5-FU + FA regimen given at less than its maximally tolerated dose.
Received: 8 May 1995 / Accepted: 25 January 1996 相似文献
3.
J. Feliu M. Gonzáles Barón J. I. Chacón E. Espinosa P. Garrido J. Castro Y. Escobar A. Colmenarejo C. Jara C. García Girón J. Espinosa A. Ordóñez 《Cancer chemotherapy and pharmacology》1996,38(2):191-194
A phase II study was performed to assess the efficacy and toxicity of the combination of cisplatin (CDDP) and tamoxifen (TAM)
in patients with metastatic malignant melanoma (MM). A total of 31 consecutive previously untreated patients with unresectable
measurable MM were given 100 mg/m2 CDDP every 21 days and 60 mg TAM every 12 h daily. All courses were given on an outpatient basis. A total of 119 courses
of treatment were given. In all, 5 of the 31 patients (16%) had an objective response (95% confidence interval 5.3 – 34%)
and 2 (6%) achieved a clinical complete response. The median duration of response was 7 months. The main side effect was gastrointestinal:
13% of the patients experienced grade 3/4 nausea/vomiting. Hematological or neurological toxicities were mild and rare. In
conclusion, the combination CDDP-TAM has limited activity in MM, although its toxicity is tolerable. Our results do not allow
us to recommend its use for the treatment of MM.
Received: 27 August 1995 / Accepted: 15 November 1995 相似文献
4.
André Planting Siang Kho Maria van der Burg H. Goey J. Schellens Martin van den Bent A. van der Gaast Maureen de Boer-Dennert Gerrit Stoter Jaap Verweij 《Cancer chemotherapy and pharmacology》1997,40(4):347-352
As a dose-response relationship has been suggested for cisplatin, it appeared attractive to explore high-dose-intensity regimens
in non-small-cell lung cancer. In a phase I study of weekly administration of cisplatin combined with oral etoposide we achieved
a cisplatin dose intensity of 52.5 – 60 mg/m2 per week in most patients. We subsequently explored this regimen in advanced non-small-cell lung cancer. Patients were treated
with cisplatin infused at 70 mg/m2 on days 1, 8, 15 and 29, 36, 43 in combination with oral etoposide given at 50 mg on days 1 – 15 and 29 – 43. Patients showing
stable disease or a better response were continued on treatment with oral etoposide given at 50 mg/m2 per day on days 1 – 21 every 28 days for a maximum of four cycles. In all, 22 patients with stage III disease and 31 patients
with stage IV disease entered the study. The median number of cisplatin administration was 6 per patient; 17 patients reached
the planned cisplatin dose intensity of 60 mg/m2 per week, 11 patients achieved 52.5 mg/m2 per week, and 7 patients reached 47 mg/m2 per week. Overall, 11 of 21 stage III patients had a partial response [response rate 51%, 95% confidence interval (CI) 36 – 81%],
as did 9 of 28 patients with stage IV disease (32%; 95% CI 15 – 49%). Toxicity was mainly hematologic, with leukocytopenia
being the most frequent cause of treatment delay. Nephrotoxicity of grade 1 was observed in seven patients. Two patients developed
clinical hearing loss. With this schedule a high median cisplatin dose intensity of 52.5 – 60 mg/m2 per week was reached. The 51% response rate achieved in stage III disease makes this schedule attractive for further exploration;
however, it is not recommended for routine use in stage IV disease.
Received: 25 August 1996 / Accepted: 20 January 1997 相似文献
5.
L. Dogliotti S. Danese A. Berruti P. Zola T. Buniva A. Bottini G. Richiardi G. Moro A. Farris M. G. Baù G. Porcile 《Cancer chemotherapy and pharmacology》1998,41(4):333-338
We assessed the activity and tolerability of a cisplatin, epirubicin, and lonidamine combination regimen as first-line chemotherapy
in 28 advanced breast cancer patients. The schedule of treatment was as follows: 60 mg/m2 epirubicin followed by 40 mg/m2 cisplatin given on days 1 and 2 every 21 days, with 450 mg lonidamine being given per os (three tablets) on days of chemotherapy
administration and in the period intervening between one cycle and the next. Patients received a median of 5 (range 1 – 6)
cycles. Overall, 22 patients were evaluable for response and 28, for toxicity. Four patients refused to continue the treatment
after the first course, one was lost to follow-up, and one died due to toxicity (septic shock). The incidence of grade 3/4
nausea and vomiting was found to be greater than that expected with epirubicin and lonidamine alone. The addition of cisplatin
resulted in an increase in platelet and hemoglobin toxicities, whereas the WBC toxicity did not differ from that expected
with epirubicin and lonidamine. The hematological toxicity was found to be cumulative, leading to treatment delay in about
50% of patients at the fifth and sixth courses. The activity of this cytotoxic regimen was noteworthy, with the overall response
rate being 81.8% (31.8% complete responses and 50.0% partial responses) in evaluable patients. This response rate decreased
to 64.2% when all registered patients were included according to an intent-to-treat analysis. In conclusion, the association
of cisplatin, epirubicin, and lonidamine given on the schedule described herein, appears to be very active but substantially
toxic. We are now testing this combination in a randomized comparison, with the cisplatin dose being reduced to 30 mg/m2 given on days 1 and 2.
Received: 1 January 1997 / Accepted: 22 July 1997 相似文献
6.
P. Pronzato Ermanno Ghio Pier Luigi Losardo Marco Landucci Franco Vaira Antonella Vigani 《Cancer chemotherapy and pharmacology》1996,37(6):610-612
A total of 32 patients with advanced non-small-cell lung cancer were treated with carboplatin (350 mg/m2, day 1) and vinorelbine (days 1 and 8) every 28 days. A response rate of 28% (95% confidence limits 12.5 – 43.7%) was observed.
The activity of this combination was demonstrated in an outpatient setting with acceptable toxicity.
Received: 6 July 1995 / Accepted: 19 October 1995 相似文献
7.
Etienne Chatelut Christine Chevreau Valérie Brunner Mathilde Martinez Georges Houin Roland Bugat Pierre Canal 《Cancer chemotherapy and pharmacology》1995,35(5):391-396
Carboplatin is an alternative for cisplatin in the treatment of urothelial cancers. A pharmacologically guided phase I study
of carboplatin in combination with methotrexate (30 mg/m2) and vinblastine (4 mg/m2) was conducted in ten patients by increment of the area under the plasma concentration versus time curve (AUC) for ultrafilterable
carboplatin using the Calvert formula. The maximal tolerated AUC was 5 mg ml-1 min, with neutropenia being the dose-limiting toxicity. There was a significant linear correlation between the percentage
of decrease in neutrophil count and the carboplatin AUC. Determination of the glomerular filtration rate by the isotopic method
allowed us to adapt the dose of carboplatin given to patients suffering from urothelial cancer, who frequently have impaired
renal function. The recommended AUC for phase II study is 4 mg ml-1 min.
Received: 9 May 1994/Accepted: 16 August 1994 相似文献
8.
Geoffrey R. Weiss John G. Kuhn Jinee Rizzo Lon S. Smith Gladys I. Rodriguez John R. Eckardt Howard A. Burris Suzanne Fields Karla VanDenBerg Daniel D. Von Hoff 《Cancer chemotherapy and pharmacology》1995,35(5):397-402
Preclinical studies of 2-chlorodeoxyadenosine (2-CdA) against solid tumors in the human tumor cloning assay and evidence
that 2-CdA is active against slow-growing or resting tumor cells have stimulated interest in the clinical activity of this
agent against solid tumors. This study sought to estimate the maximum tolerated dose, dose-limiting toxicity, and plasma and
urine pharmacokinetics accompanying the intravenous administration of 2-CdA by 120-h continuous infusion in patients with
solid tumors. Treated patients were also assessed for other toxicities of therapy and for antitumor response. A total of 23
patients received 35 courses of treatment given at doses of 3.5, 5.3, 6.5 and 8.1 mg/m2 per day by continuous intravenous infusion for 5 days and repeated every 28 days. Blood and urine specimens were collected
before, during, and after drug infusion. The dose-limiting toxicity at 8.1 mg/m2 per day manifested as granulocytopenia in 2 of 5 patients (3 of 7 courses of treatment) and as thrombocytopenia in 3 of 5
patients (3 of 7 courses of treatment). At the dose levels of 6.5 and 8.1 mg/m2 per day, recovery from thrombocytopenia was often delayed. Severe lymphocytopenia (<1,000/μl) was observed at all dose levels
of 2-CdA. Dose-related anemia and leukopenia were observed and were infrequently severe. Nonhematological toxicities were
confined to mild-to-moderate nausea, vomiting, fatigue, and anorexia. Fever of 37°–40°C was induced during drug infusion in 19 patients. No antitumor response was observed. Average plasma concentrations at steady-state
(Cpss) ranged from 3 ng/ml at the initial dose level to 13 ng/ml at the dose level of 8.1 mg/m2 per day. Both the Cpss and the area under the plasma concentration-time curve (AUC) were proportional to the dose. A relationship was observed between
the percentage of change in absolute neutrophil count and the AUC. Renal excretion accounted for only 18% of the elimination
of 2-CdA over the 5-day infusion period. The maximum tolerated dose for 2-CdA given by 5-day continuous infusion was 8.1 mg/m2 per day in this study. The recommended dose on this schedule for phase II studies is 6.5 mg/m2 per day. Granulocytopenia and thrombocytopenia were dose-limiting. No antitumor activity was observed during this study.
On the basis of the plasma concentrations of 2-CdA observed, it is unlikely that this schedule of drug administration will
permit achievement of the concentrations consistent with antitumor activity observed in preclinical studies.
Received: 14 March 1994/Accepted: 22 July 1994 相似文献
9.
A. H. Thomson Margaret Daly Janusz Knepil Paul Harden Paul Symonds 《Cancer chemotherapy and pharmacology》1996,38(6):566-570
A 62-year-old patient on long-term haemodialysis who developed an inoperable T2N3Mo squamous-cell carcinoma of the larynx was treated with weekly low-dose methotrexate (MTX) after failing to respond to radiotherapy.
The patient was initially given one dose of 10 mg MTX (6 mg/m2) as a 1-h infusion, then he received three further i. v. doses of 20 mg (12 mg/m2). Haemodialysis was performed 15 – 18 h after each dose and the patient received folinic acid (30 mg i. v. q 6 h) until the
MTX concentration was <0.1 μmol/l. The MTX concentration was measured regularly until it reached <0.1 μmol/l, and additional
samples were withdrawn pre- and post-dialysis. The MTX elimination rate constant and half-life were estimated with the patient
on and off dialysis. The patient failed to respond to treatment but did not experience MTX-related toxicity. The elimination
half-life ranged from 22 to 42 h when he was off dialysis but fell to a median of 5.5 h during dialysis. Low-dose MTX was
given to a patient on regular haemodialysis without evidence of toxicity. The rate of MTX elimination was increased during
haemodialysis, although high MTX concentrations persisted for several days and prolonged rescue with folinic acid was required.
Received: 26 November 1995 / Accepted: 20 March 1996 相似文献
10.
Yoichi Nakanishi Yuji Kawarada Nobuyuki Hirose Kiyoshi Ninomiya Masayuki Miyazaki Naoki Miyazaki Yukio Kurita Hideaki Kanegae Osamu Ohgushi Kenichi Ogata Hiroshi Yamazaki Satoru Inutsuka Nobuyuki Hara 《Cancer chemotherapy and pharmacology》1998,41(6):453-456
Purpose: A phase II trial combining cisplatin, carboplatin and etoposide was conducted in previously untreated patients with stage
IIIB and IV small-cell lung cancer, in an attempt to increase response rates and prolong survival. Methods: Previously untreated patients with small-cell lung cancer, with measurable disease, aged ≤ 72 years, performance status
≤ 2, and adequate hematologic, hepatic and renal function were enrolled in the study. They were treated with 80 mg/m2 cisplatin on day 1, 100 mg/m2 carboplatin on days 2, 3 and 8, and 50 mg/m2 etoposide on days 1, 2, 3 and 8. Results: A total of 46 patients (20 with stage IIIB and 26 with stage IV disease) were enrolled in the study. A total of 186 courses
of chemotherapy were given, and the dose was reduced in 27 courses (15%). The chemotherapy was repeated for four or more courses
in 30 patients. There were 10 complete responses and 32 partial responses, for a total response rate of 91% (95% confidence
interval, 79% to 98%). The median survival time and 2-year survival rates were 18 months and 22% for stage IIIB disease, and
14 months and 15% for stage IV disease. Major side effects were hematologic: leukopenia, anemia, and thrombocytopenia of grade
3 or more occurred in 48%, 46%, and 43% of patients, respectively. Conclusions: The three-drug regimen of cisplatin, carboplatin and etoposide is feasible and active against small-cell lung cancer.
Received: 21 May 1997 / Accepted: 11 September 1997 相似文献
11.
Matsuoka M Boku N Yoshino T Hironaka S Onozawa Y Fukutomi A Zenda S Yamazaki K Yasui H Hasuike N Inui T Yamaguchi Y Ono H Kamata M 《International journal of clinical oncology / Japan Society of Clinical Oncology》2005,10(6):429-432
A patient was diagnosed with a small cell carcinoma of the esophagus (T4N1M1b by the International Union Against Cancer [UICC]
classification) in October 2002, and initially received two courses of concurrent chemotherapy with 5-fluorouracil (5-FU;
400 mg/m2 by continuous infusion; days 1–5 and 8–12) and cisplatin (40 mg/m2 by drip infusion; days 1 and 8) and radiation therapy (2 Gy/day, days 1–5, 8–12, and 15–19; total, 30 Gy per course) with
the second course given after a 2-week interval. Two courses of chemotherapy with 5-FU (800 mg/m2; days 1–5) and cisplatin (80 mg/m2; day 1) given after this was completed. Although a complete response had been confirmed, recurrence with multiple liver and
lymph node metastases was detected 3 months after the cessation of the second course of chemotherapy. Although the patient
received second-line chemotherapy with irinotecan (150 mg/m2; every 2 weeks) from June 2003, the disease progressed. Brain metastases developed during third-line chemotherapy with gemcitabine
(1000 mg/m2 weekly by drip infusion). The symptoms were attenuated after whole-brain radiation (30 Gy), and fourth-line chemotherapy
using paclitaxel (80 mg/m2; weekly) was initiated from November 2003. A computed tomography scan 1 month after the first course of paclitaxel showed
remarkable regression of the liver metastases. The treatment strategy used for treating small cell carcinomas of the lung
may be applicable for these carcinomas of the esophagus. 相似文献
12.
A. A. Khan Judith G. Villablanca C. Patrick Reynolds Vassilios I. Avramis 《Cancer chemotherapy and pharmacology》1996,39(1-2):34-41
A phase I clinical trial of 13-cis-retinoic acid (cis-RA) was undertaken to determine the maximally tolerated dose (MTD) and pharmacokinetics (PK) of cis-RA following bone marrow transplantation (BMT) in children with high-risk neuroblastoma. Mean peak serum levels of cis-RA in 31 pediatric patients ranged from 4.9 to 8.9 μM following doses of 100–200 mg/m2 per day, divided into two doses every 12 h administered orally. The PK of cis-RA obeyed a single-compartment model following first-order absorption in the majority of patients. A linear increase in the
mean peak serum levels and area under the time-concentration curve (AUC) with increasing dose was observed. The average half-lives
of absorption and elimination were 1.0 and 5.8 h, respectively. At the MTD of 160 mg/m2 per day, the mean cis-RA peak serum concentration was 7.2±5.3 μM. AUC values were not altered significantly during a 2-week course of treatment or over a long period of multiple courses.
Levels of trans-retinoic acid, a metabolite of cis-RA, remained low but were similar on days 1 and 14, whereas the 4-oxo-13-cis-RA metabolite had increased in 64% of patients by day 14. Peak serum cis-RA concentrations correlated with clinical toxicity as grade 3 to 4 toxicity was seen in 44% of patient-courses (8/18) with
peak serum levels ≥10 μM, but only 13% (12/96) with peak serum levels <10 μM. These results show that cis-RA given at 160 mg/m2 to children achieved serum concentrations known to be effective against neuroblastoma in vitro, and the PK for cis-RA differs from that reported for trans-retinoic acid in children.
Received: 6 February/Accepted: 29 January 1996 相似文献
13.
Margaret E. Tonda Richard L. Heideman William P. Petros Henry S. Friedman Daryl J. Murry J. H. Rodman 《Cancer chemotherapy and pharmacology》1996,38(5):395-400
Purpose: The pharmacokinetic parameters and maximal tolerated systemic exposure were determined for carboplatin in young children
given in combination with cyclophosphamide and etoposide. Patients and methods: Carboplatin was administered as part of a multiagent chemotherapy regimen to 21 pediatric patients less than 5 years of
age with newly diagnosed, malignant central nervous system tumors. Patients received cyclophosphamide, 1.2 g/m2, on day 1 and carboplatin on day 2 followed by etoposide, 100 mg/m2, each day. Carboplatin doses were calculated to achieve a targeted area under the serum concentration versus time curve (TAUC)
of 5, 6.5 or 8 mg/ml . min based on each patient’s measured glomerular filtration rate (GFR). Carboplatin pharmacokinetic
parameters were determined after course 1 and then after every third course of therapy. Results: The median carboplatin clearance and GFR after course 1 were 118 and 98 ml/min per m2, respectively. Targeted doses based on measured GFR reliably achieved the TAUC for carboplatin. The median (range) carboplatin
clearance for four children less than 1 year of age was 76 (66–84) ml/min per m2, significantly lower (P=0.05) than the value of 131 (80–158) ml/min per m2 for children from 1 to 4 years of age. The mean carboplatin clearance declined by 23% in 12 patients studied from course
1 to course 4 of therapy. The decrease was greater than 20% (range 20–53%) in 7 of the 12 patients studied. Conclusion: Carboplatin clearance for children aged between 1 and 4 years at diagnosis is approximately 45% higher than previously reported
for pediatric patients, but declines after four courses of therapy. For children less than 1 year of age, carboplatin clearance
per square meter is approximately 40% lower than patients 1 to 4 years of age. There are corresponding differences in GFR
that provide a plausible explanation for the age and therapy-related changes in carboplatin clearance. Toxicity was acceptable
for patients treated at a TAUC of 6.5 mg/ml . min for carboplatin given with etoposide and cyclophosphamide. The average carboplatin
dose required for this AUC was 767 mg/m2.
Received: 13 July 1995/Accepted: 18 December 1995 相似文献
14.
Tassinari D Drudi G Panzini I Pasini G Arcangeli V Fochessati F Gianni L Mianulli AM Oliverio G Pasquini E Sartori S Ravaioli A 《International journal of clinical oncology / Japan Society of Clinical Oncology》2001,6(6):279-283
Background. Some trials have suggested that the combination of gemcitabine and platinum compounds can have a synergistic effect on several
solid tumors, but, at present, the data concerning carboplatin-gemcitabine combinations are not sufficient to allow the planning
of phase II trials. The present phase I trial was planned to define the maximum tolerated dose and the dose-limiting toxicity
of a carboplatin-gemcitabine combination.
Methods. Thirty-two patients with advanced, pretreated solid tumors were treated with carboplatin on day 1 and gemcitabine on days
1, 8, and 15 every 28 days. The starting doses of carboplatin and gemcitabine were 3.5 mg/ml per min (area under the curve;
AUC), and 600 mg/m2, respectively. The doses of the two agents were alternately increased to 4, 4.5, and 5 mg/ml per min and to 800 and 960 mg/m2, respectively. At each dose level, three patients were initially enrolled. If one of them experienced grade IV hematological
toxicity or grade III–IV nonhematological toxicity (with the exception of alopecia), an additional three patients were enrolled
at the same dose level. If two or more patients experienced grade IV hematological toxicity or grade III–IV non-hematological
toxicity (with the exception of alopecia), the maximum tolerated dose was considered to have been reached, and the dose below
this was recommended for further studies. All patients were evaluated weekly for toxicity and after every two courses of chemotherapy
for response.
Results. Dose-limiting toxicity was hematological, and the maximum tolerated doses were 4.5 mg/ml per min for carboplatin and 800
mg/m2 for gemcitabine. The activity of the carboplatin/gemcitabine combination was encouraging, with a 21.9% response rate (7/32),
three complete disease regressions, and a median time to progression of 30 weeks. The gemcitabine doses of day 15 or days
8 and 15 were omitted for hematological toxicity in 57 (50%) and 17 (14.9%) courses of chemotherapy, while no courses of chemotherapy
were delayed for grade III–IV hematological or nonhematological toxicity.
Conclusion. The maximum tolerated doses suggested by this trial are lower than those in other similar phase I trials, but they are consistent
with those reported by most of the trials investigating gemcitabine either in combination with cisplatin or in heavily pretreated
patients. Carboplatin 4.5 mg/ml per min on day 1 plus gemcitabine 800 mg/m2 on days 1, 8, and 15 every 28 days may represent a promising schedule for further phase II trials.
Received: January 29, 2001 / Accepted: September 13, 2001 相似文献
15.
Phase I clinical trial of all-trans-retinoic acid with correlation of its pharmacokinetics and pharmacodynamics 总被引:1,自引:0,他引:1
B. A. Conley Merrill J. Egorin Rajeshwari Sridhara Rebecca Finley Ramzi Hemady Suhlan Wu Nancy S. Tait David A. Van Echo David A. Van Echo 《Cancer chemotherapy and pharmacology》1997,39(4):291-299
A phase I trial of all-trans-retinoic acid (ATRA) was conducted to establish the maximum tolerable dose (MTD) of ATRA given
once daily to patients with solid tumors. Cancer patients for whom no standard therapy was available were treated with ATRA
once daily. Doses were escalated in cohorts of at least three patients. The pharmacokinetics of ATRA were assessed on day
1 for all patients and weekly for 31 patients who received doses of ≥110 mg/m2 per day. Patients were followed for toxicity and response. Correlations of toxicity frequency and grade with pharmacokinetic
parameters were sought. In addition, correlation of changes in ATRA pharmacokinetics with the concentration of ATRA metabolites
in plasma were sought. A total of 49 patients received ATRA at doses ranging from 45 to 309 mg/m2 per day. Hypertriglyceridemia was dose-limiting at 269 mg/m2 per day. Other frequent toxicities included mucocutaneous dryness and headache. With chronic dosing, plasma ATRA concentrations
fell in 59% of patients. Stable, low, or variable [ATRA] were seen in 16%, 6%, and 16% of patients respectively. Age, gender,
smoking, or concurrent medication did not correlate with the pharmacokinetic pattern. Severe toxicities tended to occur with
initial peak [ATRA] of ≥0.5 μg/ml (1.7 μM), and the toxicity frequency did not change if [ATRA] decreased with continued dosing. No consistent change in 4-oxo-ATRA
or retinoid glucuronide concentrations was observed with decreases in plasma [ATRA]. The recommended once-daily ATRA dose
is 215 mg/m2, although significant interpatient variability is observed in toxicity and plasma retinoid concentrations. Although not statistically
significant, more frequent and severe toxicity tended to occur in patients with higher plasma peak ATRA concentrations. Other
factors, such as responses at target tissues, may be at least as important as the plasma ATRA concentration in predicting
toxicity and/or response.
Received: 7 January 1996 / Accepted: 24 June 1996 相似文献
16.
Arimoto T Nakagawa S Oda K Kawana K Yasugi T Taketani Y 《Medical oncology (Northwood, London, England)》2012,29(2):1253-1254
We retrospectively evaluated the efficacy and toxicity of docetaxel and carboplatin in patients with platinum and paclitaxel-pretreated
recurrent ovarian, fallopian tube, and peritoneal cancer. Forty-two women (38 with ovarian cancer, 1 with fallopian tube cancer,
3 with peritoneal cancer) whose cancer had progressed within 12 months of their last treatment with both a platinum agent
and paclitaxel were treated with docetaxel (70 mg/m2, day 1) and carboplatin (area under the curve of 4–6, day 1). Thirty-four patients had measurable disease. The objective
response rate was 23% within 0–6 months of the progression-free interval, 50% within 6–12 months, and 32% (11 of 34 patients)
for both groups. The median time to tumor progression was 28, 49, 34 weeks, and the median overall survival time was 94, 224,
111 weeks, respectively. The most common toxicity was grade 3/4 neutropenia (98% of patients), with 15 episodes (8.4% of courses)
of neutropenic fever. The main nonhematologic toxicity was hypersensitivity; 7 patients (17%) required discontinuation of
the therapy. The results of our study indicate that the combination of docetaxel and carboplatin is effective against recurrent
ovarian, fallopian tube, and peritoneal cancer with progression-free interval of 6–12 months from previous treatment by paclitaxel
and platinum. On the other hand, single-agent chemotherapy would be better than this regimen considering its low response
rate and severe hematological toxicity for patients with progression-free interval less than 6 months. 相似文献
17.
Giorgio Vittorio Scagliotti Umberto Ricardi Lucio Crinó Ernesto Maranzano Filippo De Marinis Maria Grazia Morandi Luisa Meacci Maurizio Marangolo Ermanno Emiliani Giovanni Rosti Franco Figoli Gianfranco Bolzicco Paolo Masiero Alfonso Gentile Maurizio Tonato 《Cancer chemotherapy and pharmacology》1996,38(6):561-565
From June 1991 to August 1994, 61 patients with stage III unresectable non-small-cell lung cancer (NSCLC; 16 cases of stage
IIIA with N2 bulky disease and 45 cases of stage IIIB) were treated with ifosfamide given i.v. at 3 g/m2 on day 1, carboplatin given i.v. at 200 mg/m2 on days 1 and 2, etoposide given i.v. at 120 mg/m2 on days 1–3 (ICE) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) given s.c. at 5 μg/kg on days 4–13.
Chemotherapy was given every 3 weeks for up to three cycles and, unless the disease progressed, was followed by thoracic radiotherapy
on the tumor volume (total dose 60 Gy) and mediastinum (40 Gy). All patients had measurable or evaluable unresectable disease
and a performance status (Eastern Cooperative Oncology Group) of 0–1. Only 61% of the enrolled patients received the full
program of chemoradiotherapy according to the study design. At the end of sequential chemo-radiothera-peutic treatment, 41%
of the patients had an objective response (24 partial responses and 1 complete response), 31% showed no change and 28% had
progressive disease. The response rate noted for patients in stage IIIA with N2 bulky disease and that recorded for patients
in stage IIIB did not differ significantly. The median time to progression was 5.4 months and the median survival was 8.2
months, with the 1-year survival rate being 31%. Sites of progression were mostly intrathoracic. Haematological toxicity was
the main side effect, with grade III–IV thrombocytopenia being reported in 24% of the 165 courses of intensive ICE chemotherapy
given. Febrile neutropenia was described in six courses (three patients). Non-haematological toxicities and radiotherapy-related
side effects were generally mild and easily manageable. In conclusion, in unresectable stage III NSCLC a short program of
moderately intensified ICE chemotherapy with rhG-CSF protection followed by sequential radiotherapy failed to increase the
percentage of objective responses and reached a median survival comparable with that previously achieved with standard doses.
Received: 26 November 1995/Accepted: 5 March 1996 相似文献
18.
Altundag K Aksoy S Gullu I Altundag O Ozyar E Yalcin S Cengiz M Akyol F 《Medical oncology (Northwood, London, England)》2004,21(3):211-215
This study evaluated the efficacy and toxicity of ifosfamide and doxorubicin chemotherapy regimen in Turkish patients with
recurrent or metastatic nasopharyngeal carcinoma (NPC) previously treated with platinum-based chemotherapy. Twenty-one patients
with recurrent or metastatic NPC previously treated with platinum-based chemotherapy as adjuvant or palliative treatments
who received ifosfamide 2500 mg/m2 d 1–3, mesna 2500 mg/m2 d 1–3, doxorubicin 60 mg/m2 d 1, repeated every 21 d was retrospectively analyzed. Patients received a median number of three cycles of ifosfamide-doxorubicin
(range: 1–6). Seven patients (33.3%) achieved partial response and no patient achieved complete response. Six (28.5%) had
stable disease, whereas three (18.75%) had progressive disease. The median time to progression was 7.0 mo. Ifosfamide-doxorubicin
regimen is an effective salvage regimen in patients with recurrent and metastatic NPC. 相似文献
19.
N. Tsavaris A. Polyzos C. Kosmas J. Gogas L Giannikos 《Cancer chemotherapy and pharmacology》1997,40(4):353-357
The optimal schedule for paclitaxel administration has not yet been determined. This phase I/II study was carried out to
evaluate the safety of paclitaxel administration by 1-h infusion in the outpatient setting. A total of 43 patients with advanced
pretreated malignancies (18 breast, 18 ovarian, and 7 non-small-cell lung cancers) received at least 2 cycles of paclitaxel
given at 175 mg/m2 in a single dose by 1-h i. v. infusion. This protocol was repeated every 21 days. All patients were premedicated as follows:
promethazine given i. m. at 50 mg, dexamethasone given at 16 mg in 250 ml normal saline by i. v. infusion for 20 min and ranitidine
given i. v. at 50 mg in 250 ml normal saline over 15 min, all premedication being carried out 1 h before the paclitaxel infusion.
In a total of 156 cycles, only 1 patient presented with a hypersensitivity reaction (grade 2 urticaria in 1 cycle) and another
patient developed transient facial flushing (in 1 cycle; this was resolved by slowing of the infusion rate) on this schedule
of paclitaxel administration. Other adverse side effects were usually mild and well tolerated. Alopecia was universal; myelosuppression
was uncommon because our patients were supported with granulocyte colony-stimulating factor (G-CSF, lenograstim) given at
34 IU/day in the presence of a neutrophil count of <500 μl; neutropenia was seen in 50/156 (32%) cycles and was mild. Neurotoxicity
was the most serious adverse effect, and all patients experienced mild to severe neuromuscular toxicity, mainly in the form
of peripheral sensorimotor neuropathy and myalgias. In conclusion, 1-h paclitaxel administration is safe and reduces the duration
of treatment, making its use more convenient and easy in the outpatient setting. A prospective comparison of 1-h versus 3-h
paclitaxel infusion in terms of efficacy and toxicity is the subject of our current randomized study.
Received: 29 September 1996 / Accepted: 26 January 1997 相似文献
20.
A pharmacokinetic model and the clinical pharmacology of cis-platinum, 5-fluorouracil and mitomycin-C in isolated pelvic perfusion 总被引:2,自引:0,他引:2
Purpose: An isolated pelvic perfusion technique using multiple agents was used both in patients with unresectable recurrent pelvic
neoplasms and as a preoperative therapy for advanced pelvic malignancy. Methods: The technique consisted of vascular occlusion via transfemoral balloon catheters, circulation and drug infusion using standard
hemodialysis technology, and a 45-min isolation period. Blood and urine samples were analyzed for the levels of cis-platinum
(17 patients, 21 courses of therapy, 50–100 mg/m2, infusion 0–10 min), 5-fluorouracil (12 patients, 14 courses, 1500 mg/m2, infusion 1/3 dose 0–1 min, 2/3 dose 1–20 min) and mitomycin-C (11 patients, 14 courses, 10–20 mg/m2, infusion 10–20 min). An empirical, four-compartment pharmacokinetic model was developed to establish drug distribution curves
for the pelvic and systemic circulations and to yield valid estimates of the pharmacokinetic parameters. Results: Pelvic isolation of drug was demonstrated by the pelvic-systemic drug exposure ratios of 6.0:1 for cis-platinum, 8.4:1 for
5-fluorouracil and 9.0:1 for mitomycin-C. Isolation at the L3-4 interspace resulted in minor urine drug elimination during
isolation (cis-platinum 7.2% of drug, 5-fluorouracil 2.4% and mitomycin-C 2.5%). Because drug infusion was limited to the
first 20 min of isolation, drug levels at the end of the isolation period were reduced to the extent that no extracorporeal
drug removal mechanism was needed. Conclusion: These pharmacokinetic results indicate that this isolation technique has the potential to provide increased therapeutic
indices and is a suitable system for evaluating fast-acting highly toxic experimental drugs to human pelvic cancers which
are poorly responsive to conventional clinical protocols.
Received: 20 February 1998 / Accepted: 25 September 1998 相似文献