ABSTRACT
BACKGROUND: The purpose of this study was to evaluate the dose-limiting toxicity (DLT) and maximum tolerated dose of capecitabine when used in combination with epirubicin and cisplatin (ECC) in patients with oesophageal or gastric adenocarcinoma. Response rate, progression-free survival (PFS) and overall survival were also determined, and the effect of previous oesophago-gastric surgery or concurrent oesophago-gastric cancer on the absorption and metabolism of capecitabine was evaluated. PATIENTS AND METHODS: Patients with inoperable oesophago-gastric adenocarcinoma received up to six cycles of epirubicin (50 mg/m(2) i.v., 3-weekly), cisplatin (60 mg/m(2) i.v., 3-weekly) and capecitabine, the latter administered orally in an intermittent schedule (14 days treatment; 7-day rest period) at 3-weekly intervals. Patients were recruited into one of four escalating dose cohorts (500, 825, 1000 and 1250 mg/m(2) bd). Dose escalation occurred after six patients had completed at least one cycle of chemotherapy at the previous dose level, with DLT assessed on the toxicity of the first cycle only. Blood sampling for pharmacokinetic analyses was performed over the first 10 h of day 1 of cycle 1. RESULTS: Thirty-two patients, median age 63 years (range 32-76 years), ECOG performance status < or =2 with locally advanced (10) or metastatic (22) disease were recruited and were evaluable for toxicity. Two of five patients experienced DLT at 1250 mg/m(2) bd with grade II stomatitis (one patient) and grade III diarrhoea with febrile neutropenia (one patient). Cumulative toxicity for all cycles (n = 140) (worst grade per patient) includes grade IV oesophagitis (one patient), grade III diarrhoea (five), grade IV neutropenia with infection (seven), grade II stomatitis (four) and grade IV thrombocytopenia (one). Of 29 patients with evaluable disease, there was one complete response and six partial responses [24% response rate [95% confidence interval (CI) 10% to 44%]], a median PFS of 22 weeks (95% CI 17-27 weeks) and median overall survival of 34 weeks (95% CI 19-49 weeks). Capecitabine was rapidly absorbed after oral administration, with a t(max) of 1-2 h for capecitabine, DFCR (5'-deoxy-5-fluorocytidine) and DFUR (5'-deoxy-5-fluorouridine). The C(max) and AUC(0-)( infinity ) for capecitabine, DFCR and DFUR were similar to those observed in previous monotherapy studies of capecitabine taken after food. CONCLUSION: A dose of 1000 mg/m(2) bd of capecitabine is recommended for use on an intermittent schedule in combination with these doses and schedule of epirubicin and cisplatin. This regimen is tolerable and active in oesophago-gastric adenocarcinoma. A randomised phase III comparison with ECF is justified.
Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Deoxycytidine/analogs & derivatives , Esophageal Neoplasms/drug therapy , Palliative Care/methods , Stomach Neoplasms/drug therapy , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Capecitabine , Cisplatin/administration & dosage , Cisplatin/pharmacokinetics , Confidence Intervals , Deoxycytidine/administration & dosage , Deoxycytidine/pharmacokinetics , Dose-Response Relationship, Drug , Drug Administration Schedule , Epirubicin/administration & dosage , Epirubicin/pharmacokinetics , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Female , Fluorouracil/analogs & derivatives , Humans , Male , Maximum Tolerated Dose , Middle Aged , Neoplasm Staging , Probability , Severity of Illness Index , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Survival Analysis , Treatment Outcome , United KingdomABSTRACT
PURPOSE: N-Benzoyl staurosporine (PKC412) is a protein kinase C inhibitor with antitumor activity in laboratory models. We determined the toxicity of oral PKC412 administered daily for repeat cycles of 28 days. PATIENTS AND METHODS: Thirty-two patients with advanced solid cancers were treated at seven dose levels (12.5 to 300 mg daily) for a total of 68 cycles. RESULTS: The most frequent treatment-related toxicities were nausea, vomiting, fatigue, and diarrhea. At the two top dose levels (225 and 300 mg/d), 15 of 16 patients experienced nausea/vomiting (common toxicity criteria [CTC], version 1), grade 2 in nine of 16 and grade 3 in three of 16 patients; and six of 16 patients developed CTC grade 2 diarrhea. After 1 month of treatment, there were significant reductions in circulating lymphocyte (P <.02) and monocyte (P <.01) counts in patients receiving doses > or = 100 mg/d. Nevertheless, only two patients developed myelosuppression (both grade 2). Of two patients with progressive cholangiocarcinoma, one attained stable disease lasting 4.5 months and one a partial response lasting 4 months. There was a linear relationship between PKC412 dose and area under the curve (0-24 hours) and maximum plasma concentration with marked interpatient variability. The estimated median elimination half-life was 1.6 days (range, 0.9 to 4.0 days), and a metabolite with a median half-life of 36 days was detected. Steady-state PKC412 plasma levels at the top three dose cohorts (150 to 300 mg) were five to 10 times the cellular 50% inhibitory concentration for PKC412 of 0.2 to 0.7 micromol/L. CONCLUSION: PKC412 can be safely administered by chronic oral therapy, and 150 mg/d is suitable for phase II studies. The pharmacokinetics and lack of conventional toxicity indicate that pharmacodynamic measures may be additionally needed to optimize the drug dose and schedule.
Subject(s)
Enzyme Inhibitors/adverse effects , Neoplasms/drug therapy , Staurosporine/analogs & derivatives , Staurosporine/adverse effects , Administration, Oral , Adult , Aged , Area Under Curve , Dose-Response Relationship, Drug , Drug Administration Schedule , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/pharmacokinetics , Female , Humans , Male , Middle Aged , Staurosporine/administration & dosage , Staurosporine/pharmacokineticsABSTRACT
In vitro studies have shown a schedule-dependent synergism between Tomudex and 5-fluorouracil (5-FU). Incubation of different types of head and neck and colorectal cancer cells with levofolinic acid (LFA) plus 5-FU for 4 or 24 h, after 24-h incubation with Tomudex, produces a clear synergism. The purpose of this study was to evaluate the tolerability and activity of a combination of Tomudex, LFA, and 5-FU in advanced head and neck and colorectal cancer. Furthermore, the potential for 5-FU pharmacomodulation by Tomudex was also evaluated through an intrapatient assessment of dihydropyrimidine dehydrogenase (DPD) activity and 5-FU AUC with and without pretreatment with Tomudex. Eligible patients were treated with Tomudex at the starting dose of 1.5 mg/m2 on day 1, LFA at a fixed dose of 250 mg/m2 on day 2, immediately followed by bolus 5-FU at the starting dose of 600 mg/m2. Tomudex and 5-FU doses were alternately escalated. Courses were repeated every 2 weeks. In the second course, LFA and 5-FU were administered on day 1 and Tomudex on day 2; further treatment was given according to the sequence used in the first course. Plasma 5-FU concentrations were analyzed on courses 1 and 2 using a high-performance liquid chromatography assay with UV detection. DPD activity was measured in peripheral blood mononuclear cells on courses 1 and 2 using incubation of cytosol with [14C]FU and quantitation of metabolite formation. Fifty-eight patients were enrolled in the study. Dose escalation was stopped at step 8, because of the occurrence of dose-limiting toxicity in two of three patients. The dose level immediately before (3 mg/m2 Tomudex, 1050 mg/m2 5-FU) was selected for further evaluation. Tomudex and 5-FU mean dose intensities actually delivered at the seventh step were 1.32 and 462 mg/m2/week, respectively. Six of 40 patients with metastatic colorectal cancer obtained an objective response (15%; 95% confidence interval, 6-30%). In particular, three complete responses and three partial responses were observed. Six of 17 patients with locally advanced or metastatic head and neck cancer obtained an objective response (1 complete response + 5 partial responses; 35%; 95% confidence interval, 14-62%). Median duration of response in colorectal cancer patients was 12 months. 5-FU AUC was not significantly different between the two courses (median intrapatient difference, 9.3%; P = 0.28). DPD activity in course 1 was significantly higher than course 2 (P = 0.041) in the 16 patients in which values were evaluable. The combination of Tomudex, LFA, and 5-FU is well tolerated and active in colorectal and head and neck cancer. The Tomudex mean dose intensity actually delivered is higher than usually achieved in monotherapy. The absence of a clear pharmacokinetic interaction suggests that the synergism of Tomudex and 5-FU might occur at the cellular level.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/metabolism , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/metabolism , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/metabolism , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/enzymology , Colorectal Neoplasms/enzymology , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Head and Neck Neoplasms/enzymology , Humans , Leucovorin/administration & dosage , Leucovorin/adverse effects , Male , Middle Aged , Quinazolines/administration & dosage , Quinazolines/adverse effects , Thiophenes/administration & dosage , Thiophenes/adverse effectsABSTRACT
The three dosimetric schedules currently used in isolated limb perfusion with melphalan for malignant melanoma of the lower limb were compared in a series of 51 patients. The doses prescribed by each of the three methods (based on total body weight (TBW), limb tissue volume (LTV) and total blood volume in the perfusion circuit (TBV)) were calculated for all patients and were then compared using Wilcoxon's signed-rank test. This revealed that the method based on TBV consistently prescribed much lower doses of drug than either of the other two methods. Pharmacokinetic profiles of melphalan obtained by HPLC analysis of blood samples during the procedure also showed that the method did not reliably predict the concentration of melphalan achieved in the perfused limb. The dosimetric schedule based on LTV prescribed slightly higher doses than that based on TBW. However, the technique is more difficult to practise due to the problems of measuring the limb volume by immersion. We conclude that the dosimetric schedule based on TBW is the most appropriate by virtue of its simplicity, the high doses of melphalan which it prescribes, and the well-controlled toxicity which it produces.
Subject(s)
Antineoplastic Agents, Alkylating/administration & dosage , Chemotherapy, Cancer, Regional Perfusion/methods , Melanoma/drug therapy , Melphalan/administration & dosage , Skin Neoplasms/drug therapy , Antineoplastic Agents, Alkylating/blood , Antineoplastic Agents, Alkylating/therapeutic use , Blood Volume , Body Weight , Drug Administration Schedule , Humans , Leg/pathology , Melphalan/blood , Melphalan/therapeutic useABSTRACT
We describe melphalan pharmacokinetics in 26 patients treated by isolated limb perfusion (ILP). Group A (n = 11) were treated with a bolus of melphalan (1.5 mg kg-1), and in a phase I study the dose was increased to 1.75 mg kg-1. The higher dose was given as a bolus to Group B (n = 9), and by divided dose to Group C (n = 6). Using high performance liquid chromatography (HPLC) the concentrations of melphalan in the arterial and venous perfusate (during ILP) and in the systemic circulation (during and after ILP) were measured. Areas under the concentration time curves for perfusate (AUCa, AUCv) and systemic (AUCs) data were calculated. In all three groups the peak concentrations of melphalan were much higher in the perfusate than in the systemic circulation. The pharmacokinetic advantages of ILP can be quantified by the ratio of AUCa/AUCs, median value 37.8 (2.1-131). AUCa and AUCv were both significantly greater in Group B than in Group A (P values less than 0.01, Mann-Whitney). In Groups B and C acceptable 'toxic' reactions occurred but were not simply related to melphalan levels. Our phase I study has allowed us to increase the dose of melphalan to 1.75 mg kg-1, but we found no pharmacokinetic advantage from divided dose administration.
Subject(s)
Melanoma/drug therapy , Melphalan/pharmacokinetics , Arteries , Chromatography, High Pressure Liquid , Half-Life , Humans , Leg , Melphalan/administration & dosage , Melphalan/therapeutic use , Perfusion/instrumentation , Perfusion/methods , Time Factors , VeinsABSTRACT
Levels of melphalan (L-phenylalanine mustard) were measured in the tissues of tumour-bearing limbs treated by isolated limb perfusion (ILP). 41 samples of melanoma tissue, normal fat and skin were excised from 15 patients during ILP. A high performance liquid chromatography assay was used to measure melphalan concentrations. Levels of melphalan were higher in tumour than in fat (P < 0.01, Wilcoxon signed-ranks test), and not significantly different from levels in adjacent skin. In 2 cases there was significant regional toxicity in the treated limb, but this was not related to the levels of melphalan measured in the tissues of the limb. It is encouraging that the concentrations of melphalan which were achieved in large necrotic nodules by ILP were similar to those in well-perfused normal skin.
Subject(s)
Chemotherapy, Cancer, Regional Perfusion , Melanoma/metabolism , Melphalan/pharmacokinetics , Adipose Tissue/metabolism , Humans , Melanoma/drug therapy , Melphalan/administration & dosage , Skin/metabolism , Tissue DistributionABSTRACT
Microencapsulated mitomycin C has been used for the treatment of intrahepatic tumors in Japan, but there have been no reports of its use in western countries. In this study, the pharmacokinetic profile of intrahepatic arterial mitomycin C microcapsules is reported. Regional mitomycin C was administered to six patients, both in the microencapsulated form and in solution. The clearance (140 +/- 31 1/hour, mean +/- SD) and half-life of drug in plasma (0.39 +/- 0.03 hours), and volume distribution (246 +/- 23 1) were significantly higher, and peak drug concentrations (80 +/- 75 ng/ml) significantly lower with the microencapsulated preparation than with the free drug (clearance, 46 +/- 8 1/hour; half-life, 0.11 +/- 0.02 hours; volume distribution, 33 +/- 4; peak drug concentration, 812 +/- 423 ng/ml), on Student's t testing (P less than 0.05). The results show that very little systemic exposure is associated with the microencapsulated form of mitomycin C. Dose escalation should be feasible without increasing systemic toxicity.
Subject(s)
Antineoplastic Agents/administration & dosage , Colorectal Neoplasms , Liver Neoplasms/drug therapy , Liver Neoplasms/secondary , Mitomycins/administration & dosage , Antineoplastic Agents/pharmacokinetics , Drug Compounding , Half-Life , Hepatic Artery , Humans , Infusions, Intra-Arterial , Leukocyte Count/drug effects , Mitomycin , Mitomycins/pharmacokinetics , Platelet Count/drug effectsABSTRACT
A new syndrome of oligohydramnios, Potter's syndrome, and anuric renal failure leading to stillbirth or neonatal death from respiratory failure has recently been described. Histologically, there is renal tubular dysgenesis, especially of the proximal tubules, and apparent glomerular crowding. To date, five families have been reported, in four of which there have been affected sibs and in two parental consanguinity. The disorder is, therefore, thought to be inherited in an autosomal recessive manner.
Subject(s)
Kidney Tubules, Proximal/abnormalities , Adult , Anuria/congenital , Anuria/mortality , Anuria/pathology , Consanguinity , Female , Fetal Death , Genes, Recessive , Humans , Male , Pedigree , Pregnancy , SyndromeABSTRACT
Twelve patients were treated with didox, a new ribonucleotide reductase inhibitor, by 36 h infusion. The maximum tolerated dose was 6 g m-2, above which dose-limiting hepatic toxicity was observed. Patient tolerance was significantly better using the 36 h infusion compared to patients receiving the drug by a 30 min infusion; in particular, there were no reports of nausea or vomiting. No responses were seen in these patients. Detailed pharmacokinetics were performed at 6 g m-2 comparing the 36 h and 30 min infusions in four patients. Parent drug AUC values were lower for the 36 h infusion, 67.8 micrograms ml-1 h-1 compared to 232 micrograms ml-1 h-1 for the 30 min infusion. AUC values for the 3-hydroxy metabolite were much higher following the 36 h infusion: 55.4 compared to 18.6 micrograms ml-1 h-1. In contrast, the amide metabolite was not detected following the 36 h infusion, but AUC values of 23 micrograms ml-1 h-1 were seen after the 30 min infusion. The mean peak plasma level was 72 micrograms ml-1 following 6 g m-2 given by a 30 min infusion compared to 2.8 micrograms ml-1 following the prolonged infusion. Clearance was higher following the 36 h infusion: 97.6 versus 24.4 l h-1.
Subject(s)
Hydroxamic Acids/administration & dosage , Neoplasms/drug therapy , Ribonucleotide Reductases/antagonists & inhibitors , Adult , Aged , Drug Administration Schedule , Drug Evaluation , Female , Humans , Hydroxamic Acids/adverse effects , Hydroxamic Acids/pharmacokinetics , Infusions, Intravenous , Male , Middle AgedABSTRACT
Previous studies have demonstrated that there are circadian rhythms in susceptibility to a range of commonly used cytotoxic drugs. In this study we have compared the pharmacokinetics and myelotoxicity of carboplatin administered at 18.00 and 06.00 in random order in patients with advanced ovarian carcinoma. Carboplatin treatment at 06.00 is associated with significantly greater thrombocytopenia than at 18.00 (platelet nadir 95,000 versus 180,000, p less than 0.05). There was no pharmacokinetic difference in the patients' handling of ultrafilterable platinum therefore it is possible that there is an intrinsic rhythm of susceptibility of bone marrow to carboplatin.
Subject(s)
Bone Marrow/drug effects , Organoplatinum Compounds/toxicity , Blood Cell Count/drug effects , Carboplatin , Circadian Rhythm , Female , Hematopoiesis/drug effects , Humans , Middle Aged , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/pharmacokinetics , Ovarian Neoplasms/drug therapyABSTRACT
To assess the risk of embolism resulting from plaque fragmentation during laser angioplasty with metal-capped optical fibers, laser energy of 4, 8, and 12 W for 10 or 20 seconds was delivered through these fibers to 60 coronary endarterectomy segments fitted in a silicone tube filled with saline solution. Twenty specimens manipulated in the same way but without delivering laser energy were used as controls. The effluent was filtered through in-line filters of 225, 70, and 25 microns. Treatment with laser energy resulted in weight loss and shortening of the specimens compared to control specimens (23 +/- 4 mg versus 5.4 +/- 0.8 mg; p less than 0.001 and 0.2 +/- 0.02 mm versus 2.5 +/- 0.5 mm; p less than 0.001). However, this also produced significant debris formation for all combinations of power and time (up to 275 +/- 38 micrograms versus 155 +/- 21 micrograms in controls). Results of scanning electron microscopy showed the presence of fragments up to 300 microns in diameter. Another potential hazard of laser angioplasty with metal-capped optical fibers in thromboembolism. This was studied by delivering laser energy through metal-capped fibers during perfusion with aliquots of blood at 5 or 40 ml/min. At each flow rate nine aliquots were treated with either 4, 8, or 12 W for 3, 6, or 9 seconds and a tenth was used as a control aliquot. The effluent was filtered with five filters between 225 microns and 25 microns.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Coronary Vessels , Embolism/etiology , Lasers/adverse effects , Arteriosclerosis/therapy , Blood Flow Velocity , Fiber Optic Technology , Humans , In Vitro Techniques , Laser Therapy , Optical FibersABSTRACT
A phase 1 study of a new ribonucleotide reductase inhibitor, didox, was performed by administration of escalating doses of the drug by slow i.v. injection. Thirty-four patients with unresponsive metastatic carcinoma received the drug. There were 13 escalations of dosage, from a starting dose of 192 mg m-2 to 10 g m-2. Dose limiting toxicity was encountered at 7.5 g m-2 where disturbances of hepatic and renal function were observed, in addition to severe gastrointestinal toxicity. Pharmacokinetic studies showed that a peak level of didox was achieved within 5 minutes of injection. At 1,728 mg m-2 the data best fitted a 2 compartment open model, with a mean serum alpha t1/2 of 5.2 min, with a beta t1/2 of 41.3 min. Less than 10% of the drug was excreted unchanged in the urine and the majority of this excretion was within 6 h. Didox can therefore be safely given by slow i.v. injection at a dose of 6 g m-2.
Subject(s)
Hydroxamic Acids/therapeutic use , Neoplasms/drug therapy , Ribonucleotide Reductases/antagonists & inhibitors , Adult , Aged , Drug Evaluation , Female , Humans , Hydroxamic Acids/adverse effects , Hydroxamic Acids/pharmacokinetics , Liver Function Tests , Male , Middle Aged , Nausea/chemically induced , Neoplasm Metastasis , Neoplasms/blood , Urination Disorders/chemically induced , Vomiting/chemically inducedABSTRACT
Oestrogen receptor (ER) concentrations in breast tissues are almost universally expressed in relation to total soluble protein, though the latter does not fully correct for gross variations in receptor concentration due to variations in tissue cellularity. It was considered possible that the concentration of a specific glycolytic enzyme might be a better index and reflection of tumour cellularity. Measurements of the concentrations of lactate dehydrogenase (LDH), oestrogen receptor and total soluble protein and estimates of tumour cellularity were therefore performed on 98 breast tissues (80 breast cancers, 18 benign tissues). Cellularity and the concentrations of oestrogen receptor, lactate dehydrogenase and total soluble protein were significantly higher in breast cancers than in the benign tissues. The concentration of oestrogen receptors (positives only) was, as expected, related to tissue cellularity (correlation coefficient, r = 0.35). The concentrations of both LDH and total soluble protein were also both strongly related to tissue cellularity (correlation coefficients r = 0.67 and 0.75, respectively), and to each other (r = 0.78). These results suggest that (1) total soluble protein concentration is a good index of cellularity and (2) there is unlikely to be any additional value in expressing receptor concentrations relative to LDH since the latter appears to be a 'typical' soluble protein.
Subject(s)
Breast Neoplasms/analysis , L-Lactate Dehydrogenase/analysis , Receptors, Estrogen/analysis , Biomarkers, Tumor/analysis , Breast Neoplasms/enzymology , Breast Neoplasms/pathology , Cell Count , Female , HumansABSTRACT
We have studied the pharmacokinetics of single agent high dose cyclophosphamide (HDC) (160-240 mg kg-1) given as repeated intravenous (i.v.) infusions to six patients with small cell lung cancer (SCLC), and HDC (180 mg kg-1) combined with etoposide (750-1000 mg m-2) as repeated i.v. infusions to five patients with SCLC and two patients with teratoma. HDC has a similar pharmacokinetic profile to low dose cyclophosphamide, with a half-life of 4.83 +/- 1.3 h. Repeated administration of HDC produced a small but significant shortening of the half life (P = 0.02). The terminal half-life of high dose etoposide was 7.7 +/- 2 h which is similar to our previous results with low dose etoposide (50-300 mg m-2), but the volume of distribution which was 35.5 +/- 11.6 1. was significantly increased (P less than 0.001). Plasma steady state concentrations of 26.2 +/- 11.7 micrograms ml-1 were achieved. The possible mechanism for the alteration of volume of distribution of etoposide will be discussed.
Subject(s)
Cyclophosphamide/pharmacokinetics , Etoposide/pharmacokinetics , Carcinoma, Small Cell/drug therapy , Cyclophosphamide/administration & dosage , Drug Therapy, Combination , Etoposide/administration & dosage , Half-Life , Humans , Infusions, Intravenous , Lung Neoplasms/drug therapy , Teratoma/drug therapyABSTRACT
CHIP is a quadrivalent platinum (Pt) complex, introduced clinically as a less toxic alternative to cis-platinum. The drug's major route of excretion is via the kidneys, and in this study the pharmacokinetics of unchanged CHIP, filterable Pt and total Pt have been determined following intravenous administration to patients with a range of renal function. Total Pt and filterable Pt in plasma decayed biexponentially and was fitted to a two-compartment model, whereas unchanged CHIP declined monoexponentially and was best fitted to a one-compartment model, according to Akaike's information criteria. There is a correlation between the unchanged CHIP clearance and 51Cr-EDTA clearance. The pharmacokinetics of CHIP was determined following intraperitoneal (i.p.) administration (dose, 150-300 mg m-2 4 h dwell time) and a regional advantage (peritoneal peak concentration/plasma peak concentration) of approximately 30 fold was seen. It is likely that the dose of CHIP will need to be reduced in patients with impaired renal function, and the use of i.p. CHIP in ovarian carcinoma warrants further study.
Subject(s)
Kidney Diseases/metabolism , Organoplatinum Compounds/pharmacokinetics , Female , Humans , Infusions, Intravenous , Infusions, Parenteral , Kidney Diseases/blood , Metabolic Clearance Rate , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/blood , Ovarian Neoplasms/blood , Ovarian Neoplasms/drug therapy , Peritoneal Cavity/metabolism , Platinum/pharmacokineticsABSTRACT
The Cavitron ultrasonic surgical aspirator causes localised ultrasonic tissue fragmentation and has recently been used to remove intracranial tumours. We have examined tissue fragments from 17 operations in which the apparatus was used: in all cases a definitive diagnosis could be made from the material aspirated. This finding has not been previously described.