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 phase I study of 4'-epi-Adriamycin (4'-epi-ADM) was performed in 22 patients with various types of advanced solid tumors. Very preliminary results would indicate that the drug produces a pattern of acute toxicity which is similar to that of Adriamycin. However, the incidence of vomiting, alopecia, and marrow suppression was less pronounced than that of Adriamycin. 4'-Epi-ADM prolonged the systolic time interval, although no patient presented clinical signs of cardiotoxicity. Two patients with renal carcinoma and malignant melanoma showed objective improvement. Present results suggest that further clinical studies with 4'-epi-ADM are indicated.
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PMID:Preliminary phase I study of 4'-epi-adriamycin. 45 33

One hundred and nine adult patients with metastatic carcinoma were treated at 3-4-week intervas with a combination of adriamycin (40 mg/m2 given iv on Day 1) and cyclophosphamide (200 mg/m2/day given orally in divided doses on Days 3-6). Ninety-two of 96 patients who had an adequate trial (minumum of two courses or progression of disease after one course) had follow-up observations of tumor sites and were considered evaluable for response. Overall objective response rates by tumor type were as follows: stage III or IV ovarian adenocarcinoma, 61% (14 of 23 patients); endometrial adenocarcinoma, 67% (four of six patients); cervical adenocarcinoma, 33% (one of three patients); prostatic adenocarcinoma, 18% (two of 11 patients); testicular carcinoma, 33% (one of three patients); lung carcinoma, 21% (four of 19 patients); renal adenocarcinoma, 14% (one of seven patients); gastrointestinal adenocarcinoma, 18% (two of 11 patients); melanoma, 25% (one of four patients); and miscellaneous tumors, no responses in five patients. In patients with ovarian adenocarcinoma who had not previously received any cytotoxic chemotherapy the response rate was 80% (12 of 15 patients) with 33% five of 15 patients achieving complete clinical remission. CRs in these patients have now been maintained for periods ranging from 7 to 12 months. The major toxic effects were mild to moderate leukopenia, alopecia, and nausea with vomiting. Hemorrhagic cystitis was observed in three patients. The combination of adriamycin and cyclophosphamide is an effective treatment for carcinoma of the breast (reported elsewhere), ovary, and endometrium and should be considered for initial chemotherapy in patients with these tumors. Further investigations of its use for melanoma and carcinoma of the lung, prostate, kidney, and gastrointestinal tract are also warranted.
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PMID:Combination chemotherapy with adriamycin (NSC-123127) and cyclophosphamide (NSC-26271) for solid tumors: a phase II trial. 100 May 20

The Southwest Oncology Group (SWOG) studied the response rate and toxicity of piroxantrone (150 mg/m2 q 21 days) in patients with advanced metastatic renal cell carcinoma. Among 32 eligible patients, there were no partial nor complete responses. There were two mixed responses. Significant white cell toxicity, anemia, nausea, and vomiting were observed. Mild or moderate degrees of fever, malaise, and stomatitis occurred. No significant cardiac toxicity was noted. Piroxantrone does not have significant activity as a single agent in advanced renal cell carcinoma.
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PMID:Phase II evaluation of piroxantrone in renal cell carcinoma. A Southwest Oncology Group Study. 150 Feb 67

Spiroplatin was investigated in a multicenter phase II study, during which the drug was given over 4 h. 64 Patients with nine different solid tumors received 141 cycles of spiroplatin at a dose of 30 mg/m2 every 3 weeks. Most important side effects included nausea, vomiting, myelosuppression, and renal toxicity. Four of 11 evaluable patients with prior cisplatin developed increases in serum creatinine (3 transient, 1 died of renal failure). Of 51 patients without prior cisplatin 2 had a transient increase in serum creatinine levels, and 2 showed persistent changes, in 1 of them leading to hemodialysis. Pre- and posthydration did not reduce drug-induced nephrotoxicity. Only 3 patients showed a response; 1 with renal cell carcinoma, 1 with ovarian carcinoma, and 1 with malignant melanoma. Based on the absence of striking antitumor activity and on the presence of severe unpredictable renal toxicity, the study was stopped prematurely.
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PMID:Multicenter phase II study of spiroplatin. 157 59

We conducted a phase I study of low-dose cyclophosphamide and recombinant interleukin-2 (rIL-2) in 66 patients with advanced cancer resistant to standard therapy. All patients were evaluable for toxicity and 46 patients were evaluable for antitumor response. Patients evaluable for antitumor response included 23 with malignant melanoma, 10 with renal cell carcinoma, 4 with colon cancer, and 9 with various other solid tumors. All patients received i.v. cyclophosphamide (350 mg/m2) on day 1 followed by rIL-2 via 15 min i.v. infusion on days 4-8 and 11-15. The doses of rIL-2 ranged from 6.0 to 36.0 x 10(6) IU/m2. Each treatment cycle consisted of 21 days and a total of 113 cycles was administered. The number of treatment cycles administered per patient ranged from 1 to 8. The dose-limiting toxicities associated with rIL-2 included altered mental status, arthralgias, diarrhea, fatigue, fever, hypotension, nausea/vomiting, and peripheral edema. Twelve patients (18%) were removed from the study secondary to toxicity. Among the evaluable patients, 2 (4%) (malignant melanoma, renal cell carcinoma) developed a partial remission, 13 (29%) maintained stable disease, and 31 (67%) developed progressive disease. We conclude that the combination of low-dose cyclophosphamide and rIL-2 is tolerable in most patients but our data do not suggest an improved response rate for the combination vs. rIL-2 alone.
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PMID:Phase I study of low-dose cyclophosphamide and recombinant interleukin-2 for the treatment of advanced cancer. 159 14

Fifteen patients with advanced, measurable renal cell carcinoma entered a Phase II clinical trial of interleukin-2 (IL-2) (Teceleukin, Hoffmann-La Roche Inc., Nutley, NJ) and interferon (IFN) (Roferon A, Hoffmann-La Roche Inc.). IL-2 was administered by continuous infusion daily for 4 days and IFN was administered by intramuscular injection daily for 4 days; therapy continued for 4 weeks. Eight men and seven women were treated in this trial (median age, 61 years). Toxicity was moderate to severe with fatigue, nausea, vomiting, hypotension, and elevated blood urea nitrogen bunion and creatinine levels seen in all patients. Two patients achieved a complete remission and two patients achieved a partial remission. The median duration of response was 18 months. IL-2 and IFN is an active combination in the treatment of renal cell carcinoma and warrants further investigation.
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PMID:A phase II trial of interleukin-2 by continuous infusion and interferon by intramuscular injection in patients with renal cell carcinoma. 171 25

Fifty-four patients with advanced malignancies were treated on this phase I trial of coumarin and cimetidine. The dose of coumarin was escalated, with three patients treated at each dose level, while the cimetidine dose was held constant at 300 mg four times daily. Patients received coumarin alone as a single daily oral dose for 14 days; on day 15, cimetidine was added and both drugs were continued until progression of disease. This trial was initiated with patients receiving coumarin at 400 mg daily and closed at 7 g daily with four of five patients on this dose experiencing nausea and vomiting. Treatment was generally well tolerated over a wide range of coumarin doses. Symptomatic side effects were few, mild, and usually self limited. Side effects included insomnia, nausea, vomiting, diarrhea, and dizziness. Two patients withdrew from therapy because of daily nausea and vomiting. Typically, nausea, vomiting, and dizziness occurred 2.5-3 hours after a dose of coumarin. In most patients, these side effects abated spontaneously with continuation of therapy. There was no significant hematologic or renal toxicity. Hepatotoxicity occurred in only one patient and was manifested by asymptomatic abnormal elevations of serum hepatic transaminases. This toxicity was reversible upon interruption of therapy. Objective tumor regressions were observed in six patients with renal cell carcinoma. Responses occurred at coumarin doses ranging from 600 mg to 5 g daily. Coumarin is a relatively nontoxic, oral, outpatient therapy that warrants further investigations for the treatment of human malignancies. Because of its low toxicity, there is potential for combining coumarin with chemotherapeutic and/or biological agents in an attempt to improve on efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase I evaluation of coumarin (1,2-benzopyrone) and cimetidine in patients with advanced malignancies. 176 68

Patients (n = 15) with metastatic malignant melanoma, hypernephroma, and colon carcinoma received a three-phase adoptive immunotherapy protocol: phase 1, 10(5) units (high-dose) interleukin-2 (IL-2) iv every 8 h or 1 mg/m2 continuous intravenous infusion; phase 2, 6.5 d rest + leukapheresis; phase 3, 4 d of high-dose IL-2 plus three infusions of autologous lymphokine-activated killer cells. Toxicities of treatment included fever, chills, tachycardia, hypotension, vomiting, diarrhea, and fluid retention. Patients entering the trial were not malnourished, and mean plasma ascorbic acid concentrations before therapy were normal (36.3 +/- 14.2 mumol/L). Mean concentrations dropped by 80% after the first phase of treatment with high-dose IL-2 alone (to 7.4 +/- 4.5 mumol/L). Mean plasma ascorbic acid concentrations remained severely depleted (between 4.5 and 7.4 mumol/L) throughout the remainder of the 15-d treatment. Ascorbic acid concentrations became undetectable (less than 2.8 mumol/L) in 12/15 patients during this time. Blood pantothenate and plasma vitamin E concentrations remained within normal limits in all patients tested throughout the phases of therapy.
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PMID:Hypovitaminosis C in patients treated with high-dose interleukin 2 and lymphokine-activated killer cells. 196 85

Twenty-nine patients with biopsy-confirmed metastatic melanoma (17) or metastatic renal cell carcinoma (12) were treated with escalating doses or recombinant human interleukin-2 (IL-2) administered as weekly 24-h intravenous infusions. Patients received from 3 to 12 x 10(6) C.U./m2 (18-72 x 10(6) I.U./m2) weekly over a treatment period of 1 to 16 weeks, with a median of eight weekly cycles administered. Patients in all treatment groups experienced non-life-threatening systemic side effects consisting of fever, nausea, vomiting, fluid retention, and diarrhea. Grade III hypotension was seen in four of six patients (67%) at 12 x 10(6) C.U./m2, and represented the dose-limiting toxicity. Grade IV hypotension occurred in 1 of 14 patients at 6 x 10(6) C.U./m2; no other grade IV toxicities were observed. Grade III fever occurred in 3 of 11 patients (27%) treated at 3 x 10(6) C.U./m2, 3 of 14 patients (21%) at 6 x 10(6) C.U./m2, and 3 of 6 patients (50%) at 9 x 10(6) C.U./m2. An objective response was observed in 3 of 28 evaluable patients (10%): 1 complete response and 1 partial response in renal cell cancer, and 1 partial response in a melanoma patient. We conclude that for future studies, the recommended dose of IL-2 given as a weekly 24-h infusion is 9 x 10(6) C.U./m2 and that a low rate of objective tumor response can be obtained in patients with melanoma and renal cell carcinoma using this regimen.
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PMID:Weekly 24-hour continuous infusion interleukin-2 for metastatic melanoma and renal cell carcinoma: a phase I study. 201 99

Sixty-eight unselected patients with progressive metastatic renal cell carcinoma (RCC) were treated between March 1985 and November 1988 with continuous infusion floxuridine (FUDR). Thirty-seven percent of these patients had previously received and failed systemic treatment. Using implantable pumps for automatic drug delivery, FUDR was continuously infused for 14 days at monthly intervals. The starting dose was 0.15 mg/kg/d (intravenous [IV]; n = 61) or 0.25 mg/kg/d (intraarterial [IA]; n = 7); IV doses were increased or decreased in increments of 0.025 mg/kg/d as permitted by toxicity. Diarrhea (with or without mild abdominal cramping) and nausea/vomiting limited the FUDR IV infusion, and hepatic function abnormalities limited FUDR IA infusion. The use of a circadian-modified infusion schedule permitted high FUDR doses to be safely given as compared with a constant rate infusion schedule. Of 63 patients assessable for response, 56 received systemic FUDR infusion. Four complete responses (CRs; 7.1%); and seven partial responses (PRs; 12.5%) were observed (objective response rate, CR plus PR, 19.6 +/- 5.1% [95% confidence limits] ). The median objective response duration was 10.8 months (range, 1 to 18 months; mean, 9.4 +/- 1.6). Four additional patients had minor tumor responses (MRs; 7.1%). In a subgroup of seven assessable patients receiving hepatic arterial FUDR, we observed one CR and three PRs (57.2 +/- 42.8%). Overall, objective response (CR plus PR) was seen in a quarter of assessable patients treated, 15 of 63, while only 15 of the 63 assessable patients (25.4%) have had objective tumor progression. The median follow-up time for all 68 patients was 28 months (range, 1 to 42), and their median survival duration is 15 months (range, 3 to 37 months). Continuous infusion FUDR is an effective outpatient treatment for progressive metastatic RCC, producing durable tumor response and causing little toxicity.
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PMID:Circadian-shaped infusions of floxuridine for progressive metastatic renal cell carcinoma. 214 18


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