Cisplatin Solution Research Articles

Intratumoral Cancer Chemotherapy Through a Flexible Bronchoscope

Intratumoral Cancer Chemotherapy Through a Flexible Bronchoscope

Sustained release of cisplatin from multivesicular liposomes: Potentiation of antitumor efficacy against S180 murine carcinoma

Cisplatin was encapsulated into multivesicular liposomes (MVLs) and the entrapment efficiency, size distribution, and in vitro drug release characteristics of the cisplatin‐MVLs were studied. Pharmacokinetics, tissue distribution, and therapeutic efficacy of cisplatin‐MVLs were compared against injection of cisplatin solution into mice inoculated with the murine carcinoma 180 (S180) tumor. The results showed that the cisplatin‐MVLs were capable of high drug loading (0.148:1 mg cisplatin/mg lipid) and high encapsulation efficiency (>80%). The mean diameter of cisplatin‐MVLs was 17 μm. In vitro studies of cisplatin‐MVLs in saline solution showed that they sustained release of encapsulated drug for >7 days. Cisplatin‐MVLs showed higher drug accumulation in the liver, spleen, and tumor regions than cisplatin solution, as well as higher plasma concentrations and a longer circulation time. The therapeutic efficacy of the cisplatin‐MVL preparation against S180 tumor‐bearing mice is significantly higher than that of cisplatin solution. © 2004 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1718–1724, 2004

A randomized clinical trial of cisplatin solution and cisplatin powder combination regimens in the treatment of patients with lung cancer

To compare the efficacy and side effects between cisplatin solution and cisplatin powder combination regimens for lung cancer. A total of 223 patients were enrolled into this study. EP protocol was given to patients with small cell lung cancer (SCLC), and NP protocol to non small cell lung cancer (NSCLC). The 223 patients were randomly divided into cisplatin solution group and cisplatin powder group, and the same drugs and dosage were used in the two groups for the same type of lung cancer. Response rates of the cisplatin solution group and the cisplatin powder group were 84.8% and 82.4% for SCLC ( P > 0.05), and 31.6% and 29.9% for NSCLC ( P > 0.05), respectively. The major side effects were gastrointestinal reactions and myelosuppression. Significantly higher incidence of nausea/vomiting was found in cisplatin solution group than that in cisplatin powder group for either SCLC or NSCLC ( P < 0.05). There was a remarkable difference in cost of hospitalization between the two groups ( P < 0.05). Cisplatin solution is as effective as cisplatin powder in the treatment of lung cancer. However, the more severe nausea/vomiting reactions and higher cost of cisplatin solution should be considered in its clinical application.

Round window pH manipulation alters the ototoxicity of systemic cisplatin

The effect of manipulation of pH on the ototoxicity of systemic cisplatin was studied in Wistar rats. After control auditory brainstem responses (ABR) were performed, the auditory bullae were opened and acidic (pH 6.0), neutral (pH 7.4) or basic (pH 9.0) phosphate-buffered saline (PBS) was applied to fill the round window niche (RWN). After 30 min, 13 mg/kg cisplatin solution or saline was administered intraperitoneally. After 3 days, follow-up ABRs were performed and cochleae were processed for morphological analysis. Animals that received basic PBS on the RWN and cisplatin intraperitoneally had significantly smaller ABR threshold shifts compared to rats pretreated with neutral pH buffer ( P<0.05). Animals that received acidic PBS on the RWN and systemic cisplatin showed significantly greater ABR threshold shifts compared to those pretreated with neutral pH buffer ( P<0.05). No significant threshold changes were observed in animals that received buffer of any pH on the RWN, followed by saline intraperitoneally. Semiquantitative analysis of hair cell survival confirmed a protective effect by basic PBS against cisplatin and a synergistic effect by acidic PBS on cisplatin ototoxicity ( P<0.05). It appears that changes in cochlear pH can modulate the ototoxic effects of systemically applied cisplatin.

Cisplatin incorporated in microspheres: development and fundamental studies for its clinical application

A new drug delivery formulation, biodegradable glycolic acid–lactic acid copolymer (PGLA) microspheres incorporating cisplatin (CDDP-MS) has been developed for the treatment of peritoneal carcinomatosis. Scanning electron microscopy showed that CDDP-MS has a smooth surface and few cisplatin crystals in the hollow. An electron probe micro analyzer revealed that cisplatin was located mainly in the matrix in the state of a molecule. Release profile in vitro of CDDP from microspheres showed that the initial burst was 21.2% and the remaining CDDP was released slowly thenceforth over 14 days. Hydrolysis of CDDP-MS progresses very slowly during the 14 days, but there was no morphological change in the SEM views. The dimethylformamide content entrapped within CDDP-MS, determined by a gas chromatography, was 136 ppm at the evaporation temperature of 47 °C. The 50% lethal dose value of CDDP-MS, calculated by the Litchfield–Wilcoxon method, was reduced to 57% of the cisplatin solution. Therapeutic experiment on mice with peritoneal carcinomatosis showed that CDDP-MS did not enhance therapeutic effect as compared with the same dose dosage of a cisplatin aqueous solution but large quantities of cisplatin could be given in case of CDDP-MS owing to less toxicity.

Systemic co-treatment with α-melanocyte stimulating hormone delays hearing loss caused by local cisplatin administration in guinea pigs

It has previously been demonstrated that ototoxicity induced by systemic administration of cisplatin is reduced by concomitant administration of melanocortins, like α-melanocyte stimulating hormone (α-MSH). However, these experiments were hampered by large interanimal variability. Therefore, we re-investigated the effects of systemically administered α-MSH during local (intracochlear) administration of cisplatin. Guinea pigs, implanted with a round-window electrode, allowing daily monitoring of the compound action potentials (CAPs), and a mini-osmotic pump, pumping either 0.5 μl/h physiological saline or cisplatin solution (15 μg/ml), were co-treated daily with a subcutaneous bolus injection of either α-MSH (75 μg/kg) or physiological saline for 1 week or until the electrocochleogram showed a persistent decrease in CAP amplitude (40 dB threshold shift at 8 kHz). Next, the animals were sacrificed and the cochleas were processed for histology. After 2–3 days, cisplatin alone caused a threshold shift at all frequencies (2–16 kHz). Co-administration with α-MSH consistently delayed the criterion threshold shift by 1 day. When the 40 dB criterion had been reached, similar outer hair cell losses in both the cisplatin/α-MSH- and cisplatin/saline-treated groups were observed. This experiment confirms that direct administration of cisplatin into the cochlea results in considerably less interanimal variability than systemic administration and that co-treatment with α-MSH delays cisplatin ototoxicity. Since cisplatin was delivered directly to the cochlea, the ameliorating effect of α-MSH probably involves a cochlear target.

Influence of pH on the ototoxicity of cisplatin: a round window application study

Cisplatin is an antineoplastic agent that produces a number of dose-limiting side effects, including ototoxicity. We investigated the effect of pH on cisplatin ototoxicity. Auditory brainstem responses (ABR) were recorded in chinchillas. Then the auditory bullae were opened and acidic (pH=6.5), neutral (pH=7.4) or alkaline (pH=10.2) phosphate-buffered saline (PBS) was applied to the round window membrane. After 30 min, any remaining solution was removed and cisplatin solution was applied to the round window membrane. After 3 days, follow-up ABRs were performed and the cochleae were processed for morphological analysis. Neutral PBS+cisplatin administration resulted in profound threshold changes at all frequencies. Acidic PBS+cisplatin administration showed had a trend of increased threshold changes, but the change did not reach statistical significance. However, the degree of hair cell loss was significantly higher than that of the neutral PBS-cisplatin group. Alkaline PBS significantly reduced cisplatin-induced threshold changes ( P<0.05) compared to the neutral PBS group. Because the pH of cisplatin solution was 6.0, pH 6.0 PBS was applied to round window membrane. This acidic PBS solution did not cause any hearing impairment. These results demonstrate that pH can modulate the ototoxic effects of cisplatin.

Changes in cisplatin delivery due to surface-coated poly (lactic acid)-poly(epsilon-caprolactone) microspheres.

Smooth muscle cell proliferation plays a major role in the genesis of restenosis after angioplasty or vascular injury. Local delivery of agents capable of modulating vascular responses, have the potential to prevent restenosis. However, the development of injectable microspheres for sustained drug delivery to the arterial wall is a major challenge. We demonstrated the possibility of entrapping an antiproliferative agent, cisplatin, in a series of surface coated biodegradable microspheres composed of poly(lactic acid)poly(caprolactone) blends, with a mean diameter of 2-10 pm. The microspheres were surface coated with poly ethylene glycol (PEG), chitosan (Chit), or alginate (Alg). A solution of cisplatin and a 50:50 blend of polylactic acid (PLA)-polycaprolactone (PCL) dissolved in acetone-dichloromethane mixture was poured into an aqueous solution of PEG (or polyvinyl alcohol or Chit or Alg) with stirring using a high speed homogenizer, for the formation of microspheres. Cisplatin recovery in microspheres ranged from 25-45% depending on the emulsification system used for the preparations. Scanning electron microscopy revealed that the PLA-PCL microspheres were spherical in shape and had a smooth surface texture. The amount of drug release was much higher initially (20-30%), this was followed by a constant slow-release profile for a 30-day period of study. It has been found that drug release depends on the amount of entrapped drug, on the presence of extra cisplatin in the dispensing phase, and on the polymer coatings. This PEG or Alg-coated PLA/PCL microsphere formulation may have potential for the targeted delivery of antiproliferative agents to treat restenosis.

Intracellular targeting therapy of cisplatin-encapsulated transferrin-polyethylene glycol liposome on peritoneal dissemination of gastric cancer.

Peritoneal dissemination in gastric cancer is a common fatal clinical condition with few effective therapies available. We studied the therapeutic effect of a tumor-targeting drug delivery system that uses cisplatin-encapsulated and Tf-conjugated PEG liposomes (Tf-PEG liposomes) in nude mice with peritoneal dissemination of human gastric cancer cells. Small unilamellar Tf-PEG, PEG or DSPC/CH liposomes (bare liposomes) encapsulating cisplatin were prepared by reverse-phase evaporation followed by extrusion. Electron microscopic studies revealed that Tf-PEG liposomes were internalized into tumor cells by receptor-mediated endocytosis. To examine the biodistribution of each liposome and cisplatin level, nude mice were inoculated i.p. with 10(7) MKN45P human gastric tumor cells. On the fourth day after tumor inoculation, (3)H-CHE-labeled and cisplatin-encapsulated Tf-PEG, PEG or bare liposome were inoculated i.p. The Tf-PEG liposome-administered group maintained high liposome and cisplatin levels in ascites and showed a prolonged residence time in the peripheral circulation. Uptake of Tf-PEG liposomes into the liver and spleen was significantly lower than that of bare liposomes. Uptake of Tf-PEG liposomes in disseminated tumor cells of ascites and the greater omentum was significantly higher than that of PEG or bare liposomes and a significant increase in cisplatin levels was observed in these tumor cells. Mice receiving Tf-PEG liposomes 1 and 4 days after the day of tumor inoculation showed significantly higher survival rates compared with those receiving PEG liposomes without Tf, bare liposomes or free cisplatin solution. These results suggest that cisplatin-encapsulated Tf-PEG liposomes may be useful as a new intracellular targeting carrier for treatment of gastric cancer with peritoneal dissemination.

Nanocapsules: lipid-coated aggregates of cisplatin with high cytotoxicity.

Cisplatin is one of the most widely used agents in the treatment of solid tumors, but its clinical utility is limited by toxicity. The development of less toxic, liposomal formulations of cisplatin has been hampered by the low water solubility and low lipophilicity of cisplatin, resulting in very low encapsulation efficiencies. We describe a novel method allowing the efficient encapsulation of cisplatin in a lipid formulation; it is based on repeated freezing and thawing of a concentrated solution of cisplatin in the presence of negatively charged phospholipids. The method is unique in that it generates nanocapsules, which are small aggregates of cisplatin covered by a single lipid bilayer. The nanocapsules have an unprecedented drug-to-lipid ratio and an in vitro cytotoxicity up to 1000-fold higher than the free drug. Analysis of the mechanism of nanocapsule formation suggests that the method may be generalized to other drugs showing low water solubility and lipophilicity.

Transcatheter arterial chemoembolization therapy using iodized oil for patients with unresectable hepatocellular carcinoma

The current study was conducted to evaluate retrospectively the effects of three kinds of regimens used in transcatheter arterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC) and patients' prognosis, and to analyze their prognostic factors. The study population was comprised of 152 patients who were treated by TACE alone. Three kinds of regimens were used successively: doxorubicin hydrochloride (ADM) and mitomycin C mixed with iodized oil in 26 patients (ADMOS group), a combination of cisplatin (CDDP) solution and ADMOS in 70 patients (CDDP-ADMOS group), and CDDP powder and pirarubicin hydrochloride mixed with iodized oil in 56 patients (CTLS group). The CTLS group was comprised of patients with significantly worse background factors than the other two groups. The initial tumor response rate with a > 50% reduction was 12%, 23%, and 30%, respectively, in the ADMOS, CDDP-ADMOS, and CTLS groups. CTLS was significantly more effective than ADMOS (P < 0.05), and slightly but not significantly better than CDDP-ADMOS (P <0.1). The cumulative survival rates for the ADMOS, CDDP-ADMOS, and CTLS groups were 59.0%, 70.1%, and 72.0%, respectively, at 1 year; 0%, 16. 3%, and 29.8%, respectively, at 3 years; and 0%, 4.1%, and 16.8%, respectively, at 5 years, with median survival times of 448 days, 574 days, and 758 days, respectively. The CTLS group showed a slightly but not significantly better survival than the ADMOS and CDDP-ADMOS groups (P <0.1). Multivariate analysis indicated that the significantly important prognostic factors (in order) were extrahepatic metastasis followed by the TACE regimen, serum alpha-fetoprotein levels, and portal vein involvement and that CTLS was the best of the three regimens. Although TACE, using an effective regimen, improves clinical results, tumor factors appear to be more important when determining prognosis.

Antitumor effect of cisplatin incorporated into polylactic acid microcapsules.

Cisplatin containing microcapsules (CDDP-MC) were prepared by encapsulating cisplatin suspended in a dispersing agent in a copolymer (lactic acid) matrix using an in water drying method. Cisplatin release from the microcapsules was controlled by the addition of albumin. The CDDP-MC were relatively stable in storage, and there was only minimal initial release of the cisplatin from the microcapsules. The antitumor effects of this sustained release dosage form of cisplatin were evaluated in vitro and in vivo in mice. Mice were given an intraperitoneal (i.p.) injection of CDDP-MC 24 h after inoculation with tumor cells. The CDDP-MC were effective against Ehrlich ascites tumors and showed reduced acute toxicity compared with standard cisplatin solution. Due to the small initial release of the cisplatin from the microcapsules, however, the antitumor effect of the CDDP-MC was weaker than that of cisplatin solution. Conventional sustained release preparations have been reported to have large particle sizes and demonstrate large releases of cisplatin from microcapsules. They have been considered more effective than cisplatin solution because of the large initial release of cisplatin from the microcapsules and the maintenance of drug levels. The antitumor effect of our slow-release formulation of cisplatin was evaluated by administration of CDDP-MC 1, 4, and 7 days before i.p. implantation of tumor cells. The survival time of the tumor-bearing mice was prolonged in the CDDP-MC group, but not in the group treated with cisplatin solution. By using this modified formulation of cisplatin, the toxicity of the drug can be reduced, and effective concentrations of the drug can be maintained locally for prolonged periods of time.

Protective Effects of Betamipron on Renal Toxicity During Repeated Cisplatin Administration in Rats and Protective Mechanism

The protective effects of betamipron (BP, N-benzoyl-β-alanine) against nephrotoxicity induced by repeated cisplatin injections were examined. The ratio of the kidney weight to body weight and the lipid peroxide level after treatment with cisplatin plus BP tended to be larger and lower than those after treatment with cisplatin plus alkaline solution, respectively. The blood urea nitrogen, serum creatinine and glutathione levels in the animals treated with cisplatin plus BP differed significantly from those in the animals treated with cisplatin plus alkaline solution. Furthermore, the mechanism of the preventive effects of BP was analyzed for cisplatininduced nephrotoxicity. The concentration of cisplatin in the renal cortex significantly decreased with concomitant BP. BP inhibited the uptake of cisplatin into the renal cortex in a competitive manner in the same way as an anionic transport inhibitor, probenecid. The treatment with BP appears to be useful for the renal toxicity induced by repeated cisplatin administration.

Comparative Intravenous Toxicity of Cisplatin Solution and Cisplatin Encapsulated in Long-Circulating, Pegylated Liposomes in Cynomolgus Monkeys

The toxicity of cisplatin encapsulated in pegylated, long-circulating liposomes (SPI-077) was compared with nonliposomal cisplatin in male and female cynomolgus monkeys (n = 2-4 per sex per group) treated with intravenous infusions of 2.5 or 25 mg/kg SPI-077, 2.5 mg/kg cisplatin, placebo liposomes, or saline once every 3 weeks for total of five treatments. All animals survived until scheduled necropsy at 3 days after the final treatment or after a treatment-free 4-week recovery period. Emesis occurred after each treatment in all cisplatin-treated monkeys, but only once in one monkey treated with high-dose SPI-077. Dose-related mild decreases in red blood cell (RBC) count, hemoglobin, and hematocrit to or slightly below low normal range occurred in the high-dose SPI-077 and placebo liposome treatment groups after each treatment, with partial to complete recovery between treatments and no signs of correlating bone marrow toxicity. Decreases were similar in cisplatin-treated monkeys, but resolved only slightly between treatments and after the end of treatment (continuing to decrease in females) and were accompanied by bone marrow hypocellularity. Indirect, but not direct, bilirubin levels were cyclically elevated in the high-dose SPI-077 and placebo-treated animals, but not in the other treatment groups. Levels had either fully resolved or were near baseline and/or saline group values prior to the next treatment. Serum cholesterol levels were cyclically increased in SPI-077- and placebo liposome-treated animals, and minimally increased numbers of foam cells were seen in the liver, spleen, kidney, and other organs; both were considered related to the lipid dose administered. Cisplatin-treated monkeys exhibited sensory polyneuropathy and moderate irreversible toxic tubular nephrosis, but no neuropathy or nephrotoxicity was seen in either SPI-077 treatment group. Microscopically, treatment-related cell death was seen in dorsal root ganglia (DRG), affecting 15% of the cells in cisplatin-treated animals, compared to 8 and 12% in the low- and high-dose SPI-077 treatment groups. Neither drug was ototoxic. In summary, repeated administration of SPI-077 produced minimal, reversible effects related to the lipid dose administered, mostly limited to the 25 mg/kg dose group. The most notable effects in this group were cyclical decreases in hematology parameters thought to be related to increased recycling of a small fraction of RBCs and limited cell death in the DRG in the absence of any neurophysiological changes. Animals treated with a 10-fold lower dose of cisplatin (2.5 mg/kg), in contrast, exhibited myelo-, nephro-, and neurotoxicity, including sensory neuropathy, and were emetic after every dose. The SPI-077 liposomal formulation of cisplatin may provide a less toxic alternative to standard cisplatin solution.

Loss of in vitro cytotoxicity of cisplatin after storage as stock solution in cell culture medium at various temperatures

Cisplatin (cis-dichlorodiammineplatinum [II]) is one of the most potent and widely used cytotoxic drugs in cancer therapy. However, in vitro cytotoxicity assays often yield diverging results. Therefore, it is believed by many investigators that cisplatin is not effective in vitro. The authors investigated whether the experimental conditions used could be responsible for the diverging results. In vitro cytotoxicity assays were performed using the original cisplatin solution as distributed by the manufacturer or a 5-fold dilution of this in cell culture medium after storage for 2 weeks or 1 month at various temperatures (room temperature, 4 degrees C, and -20 degrees C). The original solution of cisplatin retained the full cytotoxic potency for at least 1 month under all storage conditions tested. The highest loss of cytotoxicity resulted from storage of cisplatin in cell culture medium in which a >7-fold increase in the concentration that inhibits 50% occurred after 2 weeks' storage at room temperature. Solutions stored in culture medium at -20 degrees C retained full cytotoxic potency. Cisplatin is a potent cytotoxic drug in vitro when stored under appropriate conditions. These findings are of relevance for in vitro studies with cisplatin.

Percutaneous intratumoral injection of cisplatin microspheres in tumor-bearing rats to diminish acute nephrotoxicity.

Poly(D,L-lactide) microspheres loaded with cisplatin (PLA-CDDP MS) were prepared by a solvent evaporation technique for direct intratumoral injection. The microspheres, 50-100 microns, containing 40.04% of cisplatin produce sustained release in vitro. PLA-CDDP MS (6 mg/kg body weight of cisplatin) suspensions were injected intratumorally into mammary tumors in rats. Cisplatin solution (6 mg/kg body weight) was injected either intratumorally or intraperitoneally in two groups. After treatments, the tumor size decreased in each of the groups as a function of time. Sixteen days post-injection, the tumors had either disappeared or significantly shrunk. PLA-CDDP MS had a similar antitumor effect compared with cisplatin aqueous solution. Blood urea nitrogen, serum creatinine and histopathology examinations revealed that the renal toxicity in the PLA-CDDP MS group was significantly less than in the control groups. These results indicate that intratumoral injection of PLA-CDDP MS maintains anticancer potency and reduces acute renal toxicity.

Cisplatin metabolites and their toxicity on isolated cochlear outer hair cells in vitro.

The exact mechanism of ototoxicity by cisplatin remains obscure. In the present study, the toxicity of cisplatin metabolites was evaluated using isolated outer hair cells of guinea pig cochlea. Cisplatin metabolites were produced by reaction of cisplatin and S9 fraction from guinea pig liver after administration with phenobarbital. The viability of the outer hair cells did not decrease after the incubation in non-metabolized cisplatin solutions or S9 fraction only, demonstrating the absence of toxic effect from non-metabolized cisplatin and the absence of intrinsic toxic substances in S9 fraction. However, metabolized cisplatin reacted with S9 fraction at 37 degrees C significantly decreased the viability. Cisplatin reacted with heat-treated S9 fraction did not produce a cytotoxic effect, suggesting an enzymatic basis for the formation of metabolites. When NADP was omitted, outer hair cells remained viable, suggesting the significant role of oxygenases in the metabolism of cisplatin. The existence of a toxic metabolites could account for the poor correlation between drug peak level and pathologic damage to the inner ear, and a delay in the onset of ototoxicity could represent the time necessary for induction of the metabolizing enzymes or for reaching a critical point in toxicity by metabolites.

Decomposition of Cisplatin in Aqueous Solutions Containing Chlorides by Ultrasonic Energy and Light

Decomposition of cisplatin in an aqueous 0.15 M chloride solution by diffuse daylight, by monochromatic light, and by ultrasonic energy was studied using a new HPLC method. The relative sensitivity of cisplatin to light copies the curve of the absorption spectrum of cisplatin with maximum at ca. 300 nm; however, any light below 500 nm must be avoided. Sonication also leads to a rapid decomposition of cisplatin. Irradiation by diffuse daylight or sonication of the cisplatin solutions for 5 min leads to ca. 1% amminetrichloroplatinate (II). Using HPLC analysis with diode‐array spectrophotometric detection, the main decomposition product was identified as amminetrichloroplatinate (II).

Selective accumulation and tumoricidal effect of cisplatin suspended in viscous ethyl oleate on hepatic cancers in animals after intraarterial infusion.

The selective accumulation and tumoricidal effects of cisplatin after intra-arterial infusion suspended in viscous ethyl oleate (VEO) on hepatic cancers of AH 272 tumor-bearing rats and VX-2 tumor-bearing rabbits were compared with those of cisplatin suspensions in ethyl oleate (EO) and Lipiodol Ultra Fluide (LP). The viscosities of VEO, EO and LP were 120, 4, and 21 centipoise (cp) respectively. Complete in vitro release of cisplatin from EO and LP occurred within 24 h, whereas only about 25% of cisplatin was released from VEO over the same period. When EO or VEO containing 3H-oleic acid were infused into the hepatic artery of rat liver inoculated with AH 272 tumor cells, radioactivity in the tumor site was higher than that in normal liver. In the case of cisplatin, concentration ratios after the infusion of EO and VEO were almost the same as those of oily carriers. Similar results were obtained in rabbit liver inoculated with VX-2 tumor cells. Cisplatin concentration in the tumor site seven days after intra-arterial infusion of VEO suspension was 5- and 1.7-fold higher, respectively, than that after EO and LP suspensions. The tumoricidal effect of cisplatin in VEO suspension on AH 272 tumor-bearing rats was higher than that after cisplatin solution and EO and LP suspensions, while VX-2 tumor growth was inhibited by the infusion of all cisplatin-containing oily carriers. VEO suspension thus appears very promising in intra-arterial infusion therapy.

Suitability of cisplatin solutions for 14-day continuous infusion by ambulatory pump

The stability of cisplatin (DDP) solutions (1 and 1.6 mg/ml in saline-mannitol) in plastic infusion bags was studied for up to 14 days at 25 degrees C, 37 degrees C and 60 degrees C. Small changes in the solution were observed, but no evidence of any decomposition product was seen. Some precipitation of DDP was seen in the 1.6-mg/ml solution at the lower temperatures. Fluid loss from the bags was significant at the higher temperatures.