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)

Based on the independent activity of cisplatin, vinblastine, and dimethyl-triazeno-imidazole-carboxamide (DTIC) (CVD), a combination of these agents was used in the treatment of patients with advanced melanoma. Vinblastine was used in a dose of 1.6 mg/m2/d for 5 days, DTIC was used in a dose of 800 mg/m2 intravenously (IV) on day 1, and cisplatin was used in a dose of 20 mg/m2/d for 4 days starting on day 2 of chemotherapy. The courses of chemotherapy were repeated at 3-week intervals. All patients were premedicated with antiemetics, and IV hydration was used before cisplatin. Fifty-two consecutive patients were registered and 50 were evaluable for response. Two patients achieved a complete response (CR) and 18 patients had a partial response (PR) for an overall response rate of 40% (95% confidence interval, 27% to 55%). The median duration of response was 9 months and the median survival time of the responders was 12 months. The overall median survival time of patients treated on this protocol was 9 months. The treatment was associated with significant toxicity consisting of nausea, vomiting, diarrhea, and partial hair loss. Additionally, neutropenia with a median nadir granulocyte count of 500/microliters was observed, and significant anemia required blood transfusions in a majority of the patients after three to four courses of chemotherapy. The dose-limiting toxicity was peripheral neuropathy which required discontinuation of cisplatin after six to eight courses of chemotherapy. We believe that this triple-drug regimen has significant activity that appears to be superior to the single-agent activity of these drugs, both in terms of increased response rate and duration of response.
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PMID:A prospective evaluation of a triple-drug regimen containing cisplatin, vinblastine, and dacarbazine (CVD) for metastatic melanoma. 280 90

Forty patients with relapsed (26) or refractory (14) myeloma were treated with epirubicin of doses of 75, 90, 105, and 120 mg/m2 in groups of 6 or more patients to test for response, maximum tolerated dose, and toxicity. Thirteen patients had received prior doxorubicin and were included in the dose findings part of the study only. Staging was I (1), II (5), and III (34). Partial responses were seen in 5 patients (18.5%) (duration 1.5, 2, 2.5, 10, and 18 months) not previously treated with doxorubicin. No responses were seen in patients treated with prior anthracycline. Responses were not dependent upon dose level of epirubicin. Median nadir white blood cell count at the four-dose levels were 2,300, 1,000, 1,600, and 1,700/mm3 with median nadir granulocyte counts of 897, 720, 688, and 192/mm3. Fever/neutropenia was infrequently observed at the three lower dose levels but occurred in 6 of 10 patients at 120 mg/m2. Platelet nadirs were 110,000, 83,000, 169,000, and 42,000/mm3. Nonhematological toxicity was not dose dependent and included alopecia (100%), nausea/vomiting (40%), and stomatitis (25%). Six patients had greater than or equal to 0.10 changes in the resting ejection fraction with one patient developing congestive heart failure that responded to medical management. This patient had received prior doxorubicin and had a history of myocardial infarction. Epirubicin can produce remissions in patients with previously treated myeloma who have not received prior doxorubicin. Since the response rate was not enhanced at 120/m2 and since fever/neutropenia was seen regularly at this dose level, the recommended dose for further study is 105 mg/m2.
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PMID:Phase I-II study of epirubicin in multiple myeloma. 316 70

High-dose doxorubicin has shown considerable activity in both previously treated and previously untreated patients with lymphoma. Because of the toxicities of doxorubicin at high dose, we elected to study a new anthracycline at doses comparable to doxorubicin at high dose, to assess response and toxicity. Epirubicin was administered at doses of 120 mg/m2, 150 mg/m2, and 180 mg/m2 every 3 weeks (maximum four doses) to groups of six patients with previously treated intermediate- and high-grade lymphoma. Sixteen of the patients had received significant prior therapy with an anthracycline and/or anthracenedione. At all dose levels, myelosuppression was severe, with median granulocyte nadirs less than 504/mm3. Hematological recovery occurred by day 21 at the 120 mg/m2 and 150 mg/m2 dose levels, allowing for the next cycle of therapy. However, at the 180 mg/m2 dose level, the majority of patients failed to have hematological recovery by the day of the next scheduled therapy. Forty-two % of patients (eight patients) had fever/neutropenia, and required antibiotics. One treatment-related septic death occurred (at 150 mg/m2). Alopecia (68%), fever immediately following treatment (63%), mild/moderate stomatitis (58%), and nausea/vomiting (53%) were the most common nonhematological toxicities. These toxicities were independent of the dose levels and were not dose limiting. A significant change (greater than or equal to 0.10) in the radionuclide ejection (EF) was seen in seven patients. The median of the entire group of patients fell from 0.63 to 0.56. No patient developed clinical or radiological evidence of congestive heart failure. A response rate of 58% (two complete responses, nine partial responses) was achieved with a median duration of 5 months (range, 1-15+). High-dose epirubicin can be successfully utilized in patients with previously treated lymphoma. The only dose-limiting toxicity observed at these dose levels was the lack of hematological recovery by day 21 with 180 mg/m2. Since epirubicin at high dose will be incorporated into high-dose anthracycline regimens in previously untreated patients utilizing a 3-week treatment cycle, 150-180 mg/m2 may be the maximally tolerated dose for such studies.
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PMID:Phase I-II trial of high-dose epirubicin in patients with lymphoma. 347 45

Eight patients with hairy-cell leukaemia (HCL) complicated by pancytopenia were treated with low dose regimens of the adenosine deaminase (ADA) inhibitor 2'-deoxycoformycin (DCF). All patients had significant haematological and clinical improvement. One patient who had been splenectomized and five patients with mild to moderate splenomegaly achieved normal blood counts within 2 months, which have been maintained for up to 18 months. Complete remissions occurred in two patients and four patients had 50-95% marrow clearance of hairy cells. The initial DCF treatments produced a 1-3 g/dl fall in the haemoglobin levels and one patient had a temporary reduction in granulocyte and platelet counts. Five patients had nausea/vomiting, and/or lethargy following DCF, but there was no correlation between the plasma levels of deoxyadenosine and adenosine and the incidence or severity of these side effects. An increased incidence of infection and drug hypersensitivity may reflect the effects of DCF on the immune system. Low dose DCF is a highly effective agent in HCL.
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PMID:The treatment of hairy-cell leukaemia with 2'-deoxycoformycin. 348 71

Seven hundred and ninety-six consecutive patients with operable primary breast cancer treated with doxorubicin-containing postoperative adjuvant chemotherapy between 1974 and 1982 were evaluated for assessment of the acute and long-term toxicities of the program. Most patients experienced nausea, vomiting, and alopecia, side effects that were totally reversible. Doxorubicin skin infiltration was observed in 6% of the patients. Hematologic toxicity was moderate, and only 26% of the patients had a granulocyte nadir of less than 1000 cells/ml. Febrile or infectious complications occurred in 6% of patients, of which 3% required hospitalization for observation and antibiotic treatment. No long-term hematologic changes were observed. Amenorrhea was reported by 80% of premenopausal patients. However, none of the patients under 30 years of age had menstrual abnormalities, whereas 96% of those 40-49 years of age developed amenorrhea. Amenorrhea was permanent for most women over 40, but for 50% of patients under 40 years of age, it was reversible. Endocrinologic studies showed that amenorrhea was a result of primary ovarian failure. The incidence of second malignant neoplasms was lower (1.3%) in the group treated with 5-fluorouracil, doxorubicin, and cyclophosphamide than in the historical control group (4.8%). Cardiac toxicity data was evaluated in 460 patients. When up to a cumulative dose of 300 mg/m2 was given, 1% of the patients developed congestive heart failure. In 4 of these 5, adequate control was achieved with medical treatment; 1 patient died as a consequence of cardiac toxicity.
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PMID:Immediate and long-term toxicity of adjuvant chemotherapy regimens containing doxorubicin in trials at M.D. Anderson Hospital and Tumor Institute. 353 81

Employment of postoperative brain irradiation in the initial management of high-grade malignant glial tumors has now become standard. The addition of conventional chemotherapy to irradiation has not significantly improved median survival beyond 1 year. We treated 25 consecutive patients (13 pilot patients and 12 protocol patients) with histologically confirmed unresectable grade 3 or 4 malignant gliomas with high-dose BCNU (carmustine) followed by autologous bone marrow transplantation and whole brain irradiation. Within 3 weeks of initial surgery, each patient had autologous bone marrow stored (median 2 X 10(8) nucleated cells/kg), and then received BCNU 1,050 mg/m2 intravenously (IV). Peripheral granulocytes recovered (greater than 500/microL) at a median of 19 days (range, 10 to 37 days), and platelets recovered (greater than 20,000/microL) at a median of 18 days (range, 13 to 40 days), following bone marrow infusion. Patients received 60 Gy whole brain irradiation when granulocytes were greater than 1,500/microL. Toxicity was well tolerated. Nausea occurred in 19 patients (76%); however, only eight patients (32%) experienced vomiting (mild in three, moderate in five). Eleven patients (44%) did not require empiric antibiotics, six of whom never developed an absolute granulocyte count less than 500/microL. Three patients with a poor performance status died early (one seizure with vomiting and asphyxiation; one, klebsiella urinary tract infection (UTI) with bacteremia; one, candidal pneumonia), and one additional patient who was performing well died of pulmonary hemorrhage. The 13 pilot patients have now been followed for a median of 23 months, with a significant survival advantage compared with the 52 consecutive historical control patients who received similar surgery and radiotherapy without high-dose BCNU (P = .037). The overall study group of 25 patients also has a significant survival advantage when compared with the same historical control group, with a projected median survival of 26 months (P = .007). This new approach using early postoperative intensive therapy consisting of high-dose BCNU, autologous bone marrow transplantation, and whole brain irradiation appears to significantly improve survival.
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PMID:Prolongation of survival for high-grade malignant gliomas with adjuvant high-dose BCNU and autologous bone marrow transplantation. 355 37

Cytotoxic chemotherapy and interferon have shown synergistic antitumor activity in vitro. The purpose of this study was to determine the maximally tolerated dose of doxorubicin given every 3 weeks, in patients receiving recombinant alpha 2-interferon [10 X 10(6) IU/m2 s.c. three times per week (Monday, Wednesday, and Friday)] during the first 2 weeks of each cycle of doxorubicin. Fourteen patients received a total of 41 cycles. Hematological toxicity was dose limiting with granulocytopenia (total granulocyte count, less than 1000) occurring in 50% of patients treated with doxorubicin at 40 mg/m2 and in 25% of patients treated with doxorubicin at 30 mg/m2. Nonhematological toxicities included a flu-like syndrome, alopecia, nausea, vomiting, diarrhea, and transient mild increases in liver function tests. A partial response was seen in one patient with metastatic squamous cell carcinoma of the skin and in another patient with metastatic adenocarcinoma of the pancreas. Concomitant administration of recombinant alpha 2-interferon given on this schedule limits the amount of doxorubicin that can be administered. However, the responses noted in this study are encouraging enough to warrant additional studies of doxorubicin plus recombinant alpha 2-interferon.
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PMID:Phase I study of alpha 2-interferon plus doxorubicin in patients with solid tumors. 375 87

Etoposide (VP-16) is a semisynthetic epipodophyllotoxin that exhibits cell cycle phase specific cytotoxicity and enhanced effectiveness with increasing duration of drug exposure. We have therefore conducted a Phase I trial to determine the side effects, tolerable doses, and pharmacokinetic parameters of VP-16 given by continuous i.v. infusion to patients with advanced cancer. Eighteen patients were treated with varying dosages of VP-16 infused continuously for 72 consecutive hours every 28 days. Using this schedule, the maximally tolerated dosage of VP-16 was 150 mg/m2/day for patients with good performance status and 125 mg/m2/day for more debilitated cancer patients. Hematological toxicity was dose limiting with median granulocyte and platelet nadirs of 700/mm3 and 116,000/mm3, respectively, at a dose of 150 mg/m2/day. Other toxicities included only mild nausea, vomiting, and alopecia. Plasma and urine VP-16 concentrations were determined using a high-performance liquid chromatography assay. At a VP-16 dosage of 150 mg/m2/day, steady-state VP-16 concentrations were in the range of 2.1 to 7.0 micrograms/ml in all patients. Further pharmacokinetic analysis revealed that the plasma clearance of VP-16 was consistently near 25 ml/min/m2 (independent of dosage) and that renal clearance accounted for only 15% of VP-16 total plasma clearance. Patient age was found to be the most important factor correlating with plasma clearance of VP-16. Linear regression analysis also revealed that both the plasma VP-16 concentration at steady state and the concentration of VP-16 in plasma at 24 h from the start of the infusion correlated with hematological toxicity; no other patient characteristics correlated with hematological toxicity. The recommended VP-16 dose for Phase II trials of 72-h continuous infusion VP-16 is 150 mg/m2/day in patients with good performance status.
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PMID:Phase I clinical and pharmacological study of 72-hour continuous infusion of etoposide in patients with advanced cancer. 381 83

10 adult patients (age 27-62 years) with refractory or relapsed acute nonlymphocytic leukemia were treated with high dose cytosine arabinoside (HDAraC: 3 g/m2 q 12 h by IV infusion, d 1-6) either alone (7 patients) or with additional treatment, consisting of bone marrow transplantation (1 patient), m-AMSA (1pt.) and VP16 (1 patient). All patients had received conventional dose AraC (CDAraC); 8 patients were resistant to CDAraC, having failed 1 or more courses of CDAraC just before treatment with HDAraC. Recovery of granulocyte count (0,5 X 10(9)L) occurred at a median of 26 d (23-27 d) after initial therapy, and recovery of platelet counts (50 X 10(9)/L) at a median of 24 d (22-27 d). 6 patients became severely septic, 3 of them requiring granulocyte transfusions. Consequently, sophisticated blood banking facilities and supportive care are required. The non-myeloid toxicities associated with HDAraC were not severe. Vomiting (9/10), erythematous skin rash (4/10), conjunctivitis and photophobia (2/10) were found most commonly. CNS-toxicity, pulmonary toxicity or drug fever were not observed. 4 patients achieved a complete remission and 1 a partial remission. 2 patients failed to respond and 3 patients died during the period of pancytopenia. Thus, HDAraC is effective treatment for refractory or relapsed ANLL, even in cases of apparent resistance to CDAraC.
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PMID:[High-dose cytosine arabinoside in the treatment of recurrent or acute refractory myeloid leukemias]. 388 19

Fourteen previously treated patients with relapsed or refractory poor-prognosis non-Hodgkin's lymphoma were given chemotherapy regimens containing high doses of cytosine arabinoside alone (seven patients) or with an anthracycline or amsacrine (seven patients). Five patients achieved a complete remission and two patients had a partial remission. The durations of remission, however, were short (median, 3 months; range, 2-6 months). Toxicities included conjunctivitis, photophobia, stomatitis, dermatitis, cerebellar dysfunction, diarrhea, nausea, vomiting, liver dysfunction, and severe myelosuppression. Recovery of an absolute granulocyte count greater than 500/microliter and an untransfused platelet count greater than 20,000/microliter required a median of 31 (range, 28-35) and 30 (range, 27-43) days, respectively. Six patients died with recurrent or residual disease before bone marrow recovery. Younger age, good performance status, and a previous complete remission were predictive of a good response. High-dose cytosine arabinoside has major myelotoxicity but significant activity in some patients with poor-prognosis non-Hodgkin's lymphoma.
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PMID:High-dose cytosine arabinoside in previously treated patients with poor-prognosis non-Hodgkin's lymphoma. 402 85


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