Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 33-year-old woman with malignant melanoma well responded to a chemotherapy including DTIC, ACNU, and VCR, and intralegional injection of OK-432. Four years prior to admission, a lentigo of 5 mm diameter at her left frontal chest was found, but, histological examination resulted in no distinctly malignant findings. In November 1979, multiple subcutaneous tumors appeared over posterior surface of the chest and left axillar region, which were gradually increasing in number and size, then she was admitted to our hospital in June, 1980. Biopsy of subcutaneous tumors revealed a malignant melanoma and its metastasis to skin. Immunochemotherapy was started immediately based upon this diagnoses. The patient received 100mg DTIC i.v. for 4 days, 100mg ACNU i.v. for one day and 1 mg VCR i.v. for one day. OK-432 was locally injected into some tumors as an immunotherapy. On completion of the third course of chemotherapy, all subcutaneous tumors were decreased in size, especially the tumors injected with OK-432. However, patient didn't respond to a repeated chemotherapy, thereafter malignant melanoma was metasized to uterus and peritoneum in May, 1981, and she died in September, 1981. Major side effects of this chemotherapy were nausea and mild transient leukocytopenia. The combination of chemotherapy including DTIC and local injection of OK-432 appeared to be effective for malignant melanoma.
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PMID:[A case of malignant melanoma responded to chemotherapy including DTIC and local injection of OK-432]. 696 31

The combination of chemotherapy and immunotherapy seems to improve response rate in metastatic melanoma. We investigated the effects on toxicity and immunological effects of a single dose of dacarbacin (DTIC; 850 mg/m2) or cisplatin (CDDP; 100 mg/m2) added to subsequent immunotherapy with interferon-alpha (IFN-alpha) and interleukin-2 (IL-2). Twelve patients, who did not respond to IFN-alpha/IL-2 alone were studied. Six received DTIC and IFN-alpha/IL-2, and six received CDDP and IFN-alpha/IL-2. DTIC did not add significant toxicity except for nausea. Significant thrombocytopenia was observed in two patients after CDDP. Although CDDP led to grade 3 nephrotoxicity in two patients, the IL-2-induced fluid retention was less severe than with IFN-alpha/IL-2 alone. Pharmacokinetics of IL-2 were not altered by DTIC, but higher IL-2 serum levels were found in patients with grade 3 nephrotoxicity after CDDP. The IL-2-related induction of secondary mediators (interferon-gamma, tumour necrosis factor-alpha, soluble CD25) was not impaired by chemotherapy and the induction of neopterin was significantly higher after addition of CDDP. One partial response was observed after addition of DTIC to IFN-alpha/IL-2, and one after addition of CDDP. The addition of a single dose of DTIC or CDDP to IFN-alpha/IL-2 is fairly well tolerated and does not abolish induction of secondary mediators. Randomized trials are necessary to test the clinical efficacy.
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PMID:Addition of dacarbazine or cisplatin to interferon-alpha/interleukin-2 in metastatic melanoma: toxicity and immunological effects. 749 66

Both chemotherapy and interleukin-2 and/or interferon-alpha produce objective responses in a proportion of advanced malignant melanoma patients. While duration of response to chemotherapy is short, i.e. usually below 4 months, immunotherapy has resulted in a small number of long-lasting remissions in patients with metastatic melanoma. In two consecutive phase II trials in a total of 67 patients, we assessed the potential synergism between both modalities, i.e. chemo- and immunotherapy. Treatment consisted of intravenous (i.v.) carboplatin (CBDCA, 400 mg/m2) and dacarbazine (DTIC, 750 mg/m2) given twice (i.v. bolus over 30 min) at 3-week intervals, or 4 cycles of DTIC (220 mg/m2 i.v. 3 days), cisplatin (DDP, 35 mg/m2 i.v. 3 days), carmustine (BCNU, 150 mg/m2 i.v. cycles 1 and 3) and tamoxifen (TAM, 20 mg oral/daily) at 3-week intervals. Chemotherapy was followed by immunotherapy with combined subcutaneous (s.c.) interleukin-2 (rIL-2) and SC interferon-alpha 2 (rIFN-alpha). Among 40 patients who received a full cycle of chemotherapy with CBDCA/DTIC and sequential immunotherapy, there were 3 (7.5%) complete remissions (CRs) with a median duration of 19 months (range 13-26+). Partial remissions (PRs) were noted in 11 (27.5%) patients with a median response duration of 8 (range 5-14) months. Among 27 patients who received DTIC/DDP/BCNU/TAM and rIL-2/rIFN-alpha, there were 3 (11%) complete remissions and 12 (44.5%) partial remissions. Duration of complete and partial remissions ranged from 9+ to 13+ (median, 11+), and 5 to 15+ (median, 7+) months, respectively. Chemotherapy produced mostly moderate toxicity. Thrombocytopenia was common with the nadir after a median time of 18 days following start of CBDCA/DTIC and DTIC/DDP/BCNU, respectively. 10 patients required transfusion of thrombocytes. Nausea and vomiting due to chemotherapy were well tolerated using concomitant ondansetrone (8 mg i.v.). Immunotherapy was self-administered at home with mild to moderate side effects; malaise, fever, chills, nausea/vomiting, diarrhoea, anorexia and arthralgias were most frequent, but were spontaneously reversible after ending rIL-2/IFN-alpha. A mean 87 and 88% of the projected doses of rIL-2 and rIFN-alpha were administered on either protocol. There were no life-threatening complications and no treatment-related deaths. The sequential combination of chemotherapy and rIL-2 plus rIFN-alpha had at least additive therapeutic activity against metastatic malignant melanoma. The schedules produced long-lasting remissions and were tolerated well overall. These trials substantiate a potential role for low to intermediate dose immunotherapy in maintaining and consolidating therapeutic effects of chemotherapy in metastatic melanoma.
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PMID:Chemoimmunotherapy of advanced malignant melanoma: sequential administration of subcutaneous interleukin-2 and interferon-alpha after intravenous dacarbazine and carboplatin or intravenous dacarbazine, cisplatin, carmustine and tamoxifen. 764 14

Human ehrlichiosis is a newly recognized tick-borne disease. Since 1935 Ehrlichia canis has been known as a cause of illness in dogs and other canine species, and for a few years it was related with human disease. In 1990, Ehrlichia chaffeensis was isolated from a man suspected of having ehrlichiosis. Partial sequencing of the rRNAS from the human isolate and E. canis, indicated that they are 98.7% related. More recently (May 1994) an "human granulocytic ehrlichiosis" have been reported in USA. PCR amplification and sequence of 16S rDNA, showed that the human isolate was virtually identical to those reported for E. phagocytophila y E. equi, organisms that cause ehrlichiosis in rumiant and in horses. Most patients shows fever, headache, malaise, nausea or vomiting, anorexia and in a minority of cases rash is present. Some of them have complications such as pulmonary infiltrates, gastrointestinal problems, renal dysfunction or failure, hepatoesplenomegaly, neurologic abnormalities, DIC and some times death. Leucopenia, thrombocytopenia and elevated liver enzyme values have been common findings. Tetracycline and cloramphenicol have been using in adults and children as especific theraphy.
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PMID:[Human ehrlichiosis. Review]. 773 23

Dacarbazine (DTIC) exerts its major biochemical effect through the formation of methylated DNA adducts. Hydroxyurea (HU) is a ribonucleotide reductase inhibitor which blocks DNA excision-repair by the depletion of intracellular ribonucleotides. Combination of HU and DTIC was used to enhance the activity of DTIC by inhibiting DNA repair. 16 patients with metastatic malignant melanoma were treated with the combination. All patients had measurable disease and none had received prior systemic therapy. Hydroxyurea was given as a continuous intravenous (i.v.) infusion of 1 g/h (total 36 g) and DTIC 1 g/m2 i.v. over 1 h, 23 h from the start of hydroxyurea infusion. 4 patients achieved partial remission with an objective remission rate of 25% [95% confidence interval (CI) 7-52%]. Median duration of response was 3.5 months. 3 of the responding patients had predominant visceral metastases. Disease was stabilised in 5 patients with a median time to progression of 16 months. The predominant toxicity to this treatment was gastrointestinal, with 3 patients developing grade 3 nausea/vomiting. Only 1 patient developed grade 3 leucopenia complicated by septicaemia. It is concluded that the combination of hydroxyurea and DTIC is a well-tolerated regimen with activity against visceral metastases from malignant melanoma but the duration of response to this treatment is short.
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PMID:A phase II study of high-dose hydroxyurea and dacarbazine (DTIC) in the treatment of metastatic malignant melanoma. 794 68

From January 1986 to April 1991, 100 consecutive patients with APL received oral ATRA at a dose of 60-100 mg/d alone or in combination with chemotherapy. In 84 cases treated with ATRA, 74 (88.1%) achieved CR; in the 16 cases treated with combined therapy, the CR Rate was 75%. Among the 50 patients followed up for a median of 36 months, 10 used ATRA (Group B) as continuation therapy, 10 chemotherapy (Group C), and 30 cases ATRA and chemotherapy alternatively (Group A). The mean survival was 8, 9, 21 months, respectively. For the 29 cases who died, the overall 3-year survival rate was higher in the group A (46.7%) than in the group B and C. ATRA did not provoke or aggravate DIC, nor did it cause bone marrow hypoplasia. The main side effects were dryness of the lip or skin, headache, nausea or vomiting and liver dysfunction. Severe scrotum exfoliative dermatitis with ulceration was seen in one case. In vitro induction of differentiation, GM-CFU, L-CFU assay and cytogenetic studies were performed. The results were discussed together with clinical observation regarding the mechanism of action of ATRA on APL. ATRA used as an inducer of differentiation is an alternative effective drug in the induction of remission in de novo APL as well as in cases in relapse.
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PMID:[Treatment of acute promyelocytic leukemia (APL) with all-trans retinoic acid (ATRA): a report of five-year experience]. 822 22

From June 1984 to October 1995, forty seven consecutive patients (pts) with a confirmed diagnosis of diffuse malignant mesothelioma (MM) of the pleura (41) and peritoneum (6), were treated with cisplatin (CDDP) (24 pts) (Group A), or Doxorubicin (ADM) (14) based chemotherapy (Group B), or a combination of CDDP and ADM (9 pts) (Group C). Chemotherapy for Group A was CDDP 100 mg/m2 Dl with Viblastine 6 mg/m2 Dl, 8 (24 pts) for Group B ADM 40 mg/m2 D I with Vincristine (VCR) 2 mg Dl and DTIC 200 mg/m2 Dl-3 (5 pts) or instead of DTIC Cyclophosphamide 600 mg/m2 Dl instead (pts 4). A Total of 11/47 (23%) of the pts responded to chemotherapy; Group A: I complete and 5 partial responders, Group B: 3 partial responders and Group C: 2 partial responders. Pts with MM of peritoneum showed I complete (Group A) and 4 partial (Group B: 2, Group B: 1, Group C: I) responses, a total of 5/6 (83%). There was no difference in survival time, duration of response and time to progression between the examined groups. A statistically significant difference between responders and non responders in terms of survival was seen: responders 20.8 (3-35), non-responders 5.05 (1-12) months (P = 0.03). Toxicity was acceptable and no treatment-related deaths occurred. Myelo-suppression, mild anemia, nausea-vomiting, anorexia and fatigue were the main toxicities. We conclude that CDDP or ADM-based chemotherapy or a combination of both drugs are equally effective in MM.
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PMID:Combination chemotherapy with cisplatin and/or doxorubicin in malignant mesothelioma. A retrospective study [corrected from prospective]. 942 83

In a multicentre phase III study of disseminated malignant melanoma performed in Sweden and Norway, 326 patients were randomised to receive treatment with the combination dacarbazine [DTIC] (D) and vindesine (V) with or without the addition of cisplatin (P). D was given intravenously (i.v.) at a dose of 250 mg/m2 days 1-5 every 4 weeks and V was given i.v. at a dose of 3.0 mg/m2 day 1 weekly. P was given i.v. at a dose of 100 mg/m2 day 1 every 4 weeks. There was no statistically significant difference in overall survival between the treatment arms (P = 0.22). Increased toxicity was observed in the treatment arm containing P of which leucopenia, alopecia and nausea/vomiting were the most pronounced. The median time to progression was significantly longer in patients treated with DVP (4.2 versus 2.2 months, P = 0.007). In conclusion, adding P to DV did not change overall survival but did significantly increase toxicity.
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PMID:Dacarbazine-vindesine versus dacarbazine-vindesine-cisplatin in disseminated malignant melanoma. A randomised phase III trial. 984 19

Inspired by the high response rates achieved with the DBCT regimen (dacarbazine [DTIC], carmustine [BCNU], cisplatin and tamoxifen [TAM]), we administered the nitrosourea compound fotemustine, cisplatin and TAM (FCT regimen) to 69 patients with metastatic melanoma. Fotemustine (100 mg/m2) and cisplatin (100 mg/m2) were administered every 4 weeks, preceded by TAM 160 mg daily for 7 days from the second course onwards. Pharmacokinetic blood sampling was performed in 14 patients during the initial two cycles to compare the pharmacokinetic behaviour of fotemustine with or without TAM. Previous chemo- or radiotherapy was allowed, and patients with brain metastases or concomitant other malignancies were included. Four complete and 11 partial responders were observed among 66 evaluable patients, yielding a response rate of 22.7% (95% confidence interval 12.9 32.5%). The median survival time was 6.4 months (range 0.1-52+ months). The main toxicities were thrombocytopenia, protracted nausea/vomiting and ototoxicity. Renal toxicity was generally mild, but possibly contributed to two deaths. Seven patients experienced deep venous thrombosis during the study. TAM had no influence on the pharmacokinetics of fotemustine. The activity of the FCT regimen was clearly inferior to that initially reported with DBCT treatment. However, a recent publication concludes that the latter achieves a considerably lower response rate when administered to a larger patient group. We believe our results reflect the true activity of FCT and similar regimens when administered routinely to unselected patients. Considering the number of potentially serious side effects, we cannot recommend the moderately active FCT regimen as a palliative treatment option for melanoma patients.
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PMID:Clinical experience of fotemustine, cisplatin and high dose tamoxifen in patients with metastatic malignant melanoma. 991 19

Melanoma is an uncommon disease in Japan. The incidence, however, has been gradually increasing in the last two decades, as in many other countries worldwide. Ten patients with metastatic malignant melanoma were treated between March of 1997 and April of 1998 in the Department of Dermatology, National Cancer Center Hospital, with a combination chemotherapy consisting of dacarbazine (DTIC), nimustine hydrochloride (ACNU), cisplatin (CDDP), and tamoxifen (TAM). The patients characteristics were as follows: four were males and six females; the age range was 33-70 years; all were Japanese; sites of primary disease: extremities 4, primary unknown 3, nasal cavity 1, anus 1, scalp 1; sites of metastases: lymph nodes 6, pulmonary system 5, skin 2, liver 3, gall bladder 1, adrenal gland 1. The chemotherapy regimen included DTIC 220 mg/m2/i.v. on days 1 through 3, ACNU 60 mg/m2/i.v. on day 1, cisplatin 25 mg/m2/i.v. on days 1 through 3, and tamoxifen 10 mg p.o. twice daily. One patient achieved a complete response and 3 showed partial responses. The response rate was 40%. The four responders included those with metastases to the nodes, lung, and liver. The main toxicities were nausea, vomiting, leucopenia, anemia, and thrombocytopenia. This regimen is a fairly effective combination against metastatic melanoma.
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PMID:Dacarbazine, nimustine hydrochloride, cisplatin and tamoxifen combination chemotherapy for advanced malignant melanoma. 1048 2


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