Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A combination of cisplatin and cytosine arabinoside was used to treat 21 patients with glioblastomas and 5 patients with recurrent grade II gliomas. Cisplatin 60-100 mg/m2 was given I.V. in 250 ml 0.45% saline and preceded by 500 ml dextrose 5% in 0.45% saline. Mannitol 50 g was given I.V. concurrently with the cisplatin. Cytosine arabinoside 500-1000 mg/m2 was given by rapid I.V. infusion immediately after the cisplatin. Of 25 evaluable patients, 10 (40%) experienced objective tumor shrinkage on CT scan, and 6 (24%) stabilized. There were 2 complete remissions. Patients who had had no prior treatment had a higher response rate (58%) than those previously treated (23%). Myelosuppression occurred in some patients 2-3 weeks after treatment. Gastrointestinal toxicity (vomiting and diarrhea) was dose-limiting. Two patients had possible neurological toxicity. Recommended doses for further studies are cisplatin 90 mg/m2 and cytosine arabinoside 900 mg/m2.
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PMID:Cisplatin plus cytosine arabinoside in adults with malignant gliomas. 608 23

A prospective randomized study was conducted to determine the relative effectiveness, toxicity and tolerance of methotrexate (MTX) versus cisplatin (DDP) in patients with recurrent head and neck squamous cell carcinoma. Forty-four patients were randomized to receive either MTX, 40 mg escalated to 60 mg/m2 IV push weekly, or DDP, 50 mg/m2 6 hour infusion days 1 and 8 every 4 weeks. All patients had objectively measurable disease and a performance status greater than 60% (Karnofsky scale). All had been treated with surgery and/or radiotherapy. No patients had prior chemotherapy. Prior treatment, performance status, and site of primary disease were comparable in both groups. Complete and partial objective responses were achieved in 23.5% of the MTX group and 28.6% of the DDP group (P = 0.51). Median duration of response was 84 days in the MTX group and 92 days in the DDP group. Median survival of patients was 6.1 months with MTX and 6.3 months with DDP. Mucositis was noted in 38% of patients in the MTX group (P = 0.001) compared to none in the DDP group. Vomiting occurred in 87% of patients in the DDP group (P less than .0001) compared to 10% of patients in the MTX group. This study demonstrates that in the treatment of recurrent head and neck squamous cell carcinoma, MTX and DDP are equally effective, although MTX appears to be better tolerated.
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PMID:A prospective randomized trial of methotrexate versus cisplatin in the treatment of recurrent squamous cell carcinoma of the head and neck. 619 May 45

Four patients with small residual ovarian carcinoma following treatment with cisplatin, doxorubicin, and cyclophosphamide have subsequently received 57 courses of ip cisplatin. Cisplatin (120-270 mg in 2 L of Ringer's lactate) was administered via Tenckhoff catheter, with a dwell time of 15-20 mins. Courses were given weekly for 12 weeks, with response documented by laparoscopy or laparotomy prior to and following the trial. With a dwell time of 20 mins, 75% +/- 5% (mean +/- SD) of platinum was recovered. With 120 mg of cisplatin and a dwell time of 20 mins, total plasma platinum peaked at 1.23 +/- 0.42 microgram/ml and by 8 hrs decreased to 0.67 +/- 0.12 microgram/ml. Filterable (non-protein-bound) platinum peaked at 0.73 +/- 0.21 microgram/ml and by 8 hrs fell to 0.03 microgram/ml. Excretion rate paralleled the filterable plasma curve, peaking at 40 mins; 30% +/- 7% of absorbed drug was recovered in urine within 24 hrs. Renal clearance of filterable platinum was 106 +/- 20 ml/min. Creatinine clearance was 76 +/- 7 ml/min. Three responses, one complete and two partial, were noted. Zero to two episodes of vomiting occurred in each course. One patient had a creatinine clearance decrease to 40 ml/min, one had two episodes of thrombocytopenia, and one had mild abdominal pain with a cisplatin dose of greater than or equal to 210 mg. No neurotoxicity, catheter infection, or peritonitis was encountered.
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PMID:Pharmacokinetics of Ip cisplatin in refractory ovarian carcinoma. 622 94

The comprehensive emetic response to xenobiotics can be quantified by monitoring the physiological forces which effectuate vomiting. A unique sequence of thoracic pressure pulses, generated by the somatic muscles of ventilation, can be measured by means of a central venous catheter. This unambiguous emetic endpoint is used to record emetic latency, repetitions and duration of action, all on an established time base and dependent of stomach content. Deslanoside (160 micrograms/kg) produced emesis in 15 cats beginning in 4.4 +/- 1.9 min (mean +/- S.D.). Subsequent emetic episodes were related in time in a log-linear but biphasic manner. Cisplatin (7.5 mg/kg) had an emetic latency of 71 +/- 18 mn in 7 cats. Additional events also had a long-linear temporal relationship for up to 400 min. This quantified emetic profile of cisplatin served as a measure for assessing antiemetic activity of N-metyllevonantradol (Pfizer), nabilone (Lilly) and prochlorperazine. The cannabinoids all evinced dose dependent antiemetic activity in terms of either complete protection, or increased latency to the first emetic episode and reduced number of episodes in those animals not completely protected. By comparison prochlorperazine afforded only minimal protection.
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PMID:Antiemetic activity of N-methyllevonantradol and nabilone in cisplatin-treated cats. 627 34

Marijuana has been used for over 2 centuries. Its major psychoactive constituent, delta-9-tetrahydrocannabinol (THC) was isolated in 1964 and first used to control nausea and vomiting during chemotherapy in the 1970s. THC has cardiovascular, pulmonary and endocrinological effects as well as actions on the central nervous system. Alterations in mood, memory, motor coordination, cognitive ability, sensorium, spatial- and self-perception are commonly experienced. The precise antiemetic mechanism is unknown. THC and nabilone act at a number of sites within the central nervous system. Cannabinoids have also been shown to inhibit prostaglandin synthesis in vitro. In controlled clinical trials, THC is superior to placebo and prochlorperazine in antiemetic effectiveness. Effectiveness of THC correlates to a 'high' experienced by the patient. A variety of chemotherapy regimens respond to THC including high-dose methotrexate and the doxorubicin, cyclophosphamide, fluorouracil combination. Cisplatin is more resistant. Side effects are generally well tolerated but may limit THC use in the elderly or when high doses are administered. Nabilone, a synthetic cannabinoid, is also an effective antiemetic which is more active than prochlorperazine in preventing chemotherapy-induced emesis, including cisplatin-containing regimens. Side effects are similar to THC and may be dose-limiting. Levonantradol, another synthetic cannabinoid, is an effective antiemetic. It may provide more flexibility in the outpatient setting since it can be administered orally or intramuscularly. Most side effects are mild except for dysphoria which may be dose-limiting.
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PMID:Review of cannabinoids and their antiemetic effectiveness. 630

Since the discovery of the antitumor activity of cis-dichlorodiammine platinum (II) in various tumor systems by B. Rosenberg in 1969, many Pt complexes have been prepared to ameliolate DDP. It has been known to have severe nephrotoxicity, nausea and vomiting, as well as ototoxicity. However, DDP has a wide spectrum of antitumor activity, and it is specifically active against cancers in bladder, testis, ovary and, head and neck. To attenuate such toxicities, hydration prior to DDP administration and/or application of diuretics, as well as combination therapy with other antitumor agents have been developed. Various studies indicated that the nephrotoxicity was attenuated by changing carrier ligands and leaving groups. Toxicity to be removed so far is myelosuppression and vomiting. Another problem is the cross-resistance of DDP. Against L1210/DDP, amine, ethylenediamine, o-phenylenediamine and 1,2-cyclopentanediamine Pt complexes showed cross-resistance, while dach and 1,2-cycloheptanediamine Pt complexes showed no cross-resistance. In this review, the author discusses mainly preparation of the Pt complex of the 2nd generation, being now in the clinical trials and my approach to the development of the antitumor Pt complexes in my laboratory. Pt complexes being now in the advanced studies are: CBDCA, CHIP, DACCP, PYPl PHIC, TNO-6 and l-OHP. New Pt complexes are still deviced continuously. The capability of synthesizing Pt complexes which are characteristically effective against the slow-growing solid tumors, from the standpoint of the coordination chemist.
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PMID:[Development of antitumor platinum complexes]. 636 50

Cisplatin-induced emesis was characterized using the cat as an experimental model. The incidence, latency, and number of vomiting episodes which occurred over an 8-hour period were determined for iv doses ranging from 3 to 10 mg/kg. Oscillographic recording of physiologic pressures which produce vomiting served to document the observation that 7.5 mg/kg iv was the most effective dose. This dose produced vomiting in seven animals with a latency of 71 +/- 7.04 minutes (mean +/- SE) and subsequent emetic episodes (averaging 3.86/animal) followed a linear relationship with respect to the logarithm of time. The larger dose of 10 mg/kg appeared to be less effective, because not all animals responded. Those animals that vomited in response to this dose did so only after a significantly increased latency. Four animals with longstanding lesions of area postrema were tested with cisplatin (7.5 mg/kg); all four failed to vomit during a 6-hour observation period. In addition, none of the animals exhibited the sustained malaise associated with cisplatin administration to intact animals and only one displayed any prodromal emetic signs. These findings demonstrate that the area postrema, the anatomic site of the chemoreceptor trigger zone for emesis, is essential for cisplatin-induced vomiting. Elucidation of this action suggests a possible mechanism for other emetogenic anticancer agents.
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PMID:Cisplatin-induced vomiting eliminated by ablation of the area postrema in cats. 653 13

Experiences with cis Platin therapy in cases of ovarian cancers after previous tumorchemotherapy are reported. 23 patients were treated with 100 mg cis Platin (DDP)/m2 (Lachema, CSSR, Brno) in intervals of four weeks following extensive hyperhydratation. We observed following therapeutic effects: CR 4 of 23 pat., PR 11 of 23 pat., NC 3 of 23 pat. and progression in 5 cases. The average remission-time was the best in cases with CR (8,3 month) and the worst in cases without any therapeutic effect (1 month). Side effects observed: severe vomiting was compulsory in all cases. Twice we observed neuro- and ototoxicity after the 5th respectively 6th cyclus. DDP is an effective but also toxic cytostatic drug for treatment of ovarian cancer in the 2nd or 3rd line. It should be used in cases of secondary resistant tumours.
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PMID:[Experiences with cisplatin (Platidiam) chemotherapy in secondary resistant ovarian carcinomas]. 653 71

Rosenberg et al discovered in the coordination complexes of platinum a new, novel type of potential antitumor agent. Cisplatin [cis-dichlorodiammine platinum (II)4 proved active against a variety of rodent tumors and acted synergistically when combined with other chemotherapeutic agents. Initial clinical tests by Hill et al in 1971, showed cisplatin to be active against malignant lymphoma, Hodgkin's disease, and certain other malignancies. Significant nephrotoxicity, nausea, and vomiting were noted. Since then, cisplatin has been tested alone and in combination chemotherapy and has proven an efficacious anticancer agent in squamous cell carcinoma of head and neck, ovarian carcinoma, disseminated testicular cancer, and others. Its therapeutic value was acknowledged when approved in 1978 by the U.S. FDA for treatment of the latter cancer. The current clinical literature indicates clearly that the full potential of this drug has not yet been realized. Hydration and diuresis have served to mitigate much of the nephrotoxicity, while significant strides toward amelioration of the nausea and vomiting have also been achieved. Literally, thousands of chemically-related congeners have been synthesized, and many have shown marked potency against rodent tumors. Very few, however, have been evaluated clinically, vis-a-vis malonato trans(-)-1,2-diaminocyclohexane platinum(II); this appears a most promising and fertile area of future investigation.
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PMID:Organo-platinum complexes as antitumor agents (review). 675 Dec 11

Phase I study of cis-diamminedichloroplatinum(II) (CIS-DDP) was performed in 7 institution's clinical group using 40 patients with histologically proven urologic and gynecologic malignancies. The most characteristic adverse effects were nausea, vomiting, and anorexia. With the cessation of administration they disappeared within one or two days. Manifestation of hematopoietic and renal toxicities were found low. Hepatotoxicities were slight. In this study there were no cases who showed hearing disturbances and tinnitus, which were reported in rather high percentages. Acceptable doses of CIS-DDP for single and 5 days' consecutive administration were estimated 50 and 20 mg/m2/day respectively.
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PMID:[Phase I study of a new antineoplastic agent, cis-diamminedichloroplatinum (II)]. 689 90


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