Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0854467 (myelosuppression)
 5,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In an attempt to improve upon the 43%-48% regression rates noted for various CAP regimens consisting of cyclophosphamide, doxorubicin (Adriamycin), and cis-diamminedichloroplatinum(II) in various doses and schedules, triazinate was added to that three-drug combination, and the new combination (T-CAP) was evaluated in patients with advanced adenocarcinoma of the lung. T-CAP produced a regression rate of 57% with a 7-week increase in overall median time to progression and a 4-week increase in overall median survival compared to the best of the CAP schedules. More stomatitis and dermatitis were noted with the new combination, but myelosuppression was similar to that of the CAP regimens. These data suggest that further studies with triazinate should be conducted in patients with adenocarcinoma of the lung.
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PMID:Phase II evaluation of the combination of triazinate, cyclophosphamide, doxorubicin, and cis-diamminedichloroplatinum(II) in patients with advanced adenocarcinoma of the lung. 719 2

Maytansine, a new ansa macrolide antitumor antibiotic, was administered to a total of 107 patients in a Phase I-II study. Dose-limiting toxic reactions which occurred at 0.75-1.0 mg/M2 in both Phase I and II were neurologic and consisted primarily of lethargy/weakness (a debilitation syndrome) and paresthesias. Gastrointestinal and neurologic toxic reactions increased in frequency and severity as a function of dose. Myelosuppression, while infrequent, occurred only in previously treated patients. Changes in liver function tests were subclinical. Two partial remissions were observed at a dose-level of 0.5 mg/M2 in Phase I:1 patient with squamous cell carcinoma of the lung responded for five weeks, while the other patient with adenocarcinoma of the lung responded for four weeks. One partial remission, lasting 14 weeks was seen in Phase II in a patient with malignant melanoma treated at dose-level of 1.0 mg/M2. All responses were in heavily pretreated patients. pairs of small bowel biopsy specimen used to define the mitotic index demonstrated peak mitotic arrest at 24 hours in contrast to vinca alkaloids which appear to have a peak mitotic arrest at 12-24 hours.
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PMID:A phase I-II study of maytansine utilizing a weekly schedule. 721 95

PALA was given iv on a weekly schedule to 32 patients with advanced malignant tumors. A course of treatment consisted of three weekly doses. Patients were treated at eight dose levels, ranging from 900 to 6750 mg/m2. Gastrointestinal toxicity (diarrhea) and skin rash were dose-limiting. No consistent myelosuppression occurred, and no renal or hepatic toxicity was observed. Two patients who did not have metastatic intracranial disease experienced episodes of encephalopathy and seizures. No major therapeutic responses were observed during this phase I trial; however minor responses (greater than or equal to 25% tumor decrease) occurred in three patients (one with adenocarcinoma of the lung and two with epidermoid carcinoma of the bladder). Doses of 4500 mg/m2/week for patients with a performance status greater than or equal to 70 and 3750 mg/m2/week for patients with a lower performance status are recommended for phase II studies.
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PMID:Phase I trial of PALA. 747 Nov 20

cis-Bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum(II) (NDDP) is a lipophilic non-cross-resistant platinum compound formulated in large multilamellar liposomes (1-3 micrometer). The maximum tolerated dose (MTD) of liposomal-entrapped NDDP (L-NDDP) administered i.v. in humans is 300 mg/m2, and myelosuppresion is the dose-limiting toxicity. L-NDDP administered i.p. is absorbed slowly from the peritoneal cavity of rats. Recently, i.p. cisplatin has been shown to be superior to i.v. cisplatin in improving the survival of patients with ovarian carcinoma and minimal residual disease. We conducted a Phase I study to determine the MTD, side effects, kinetics of absorption into the systemic circulation, and preliminary antitumor activity of L-NDDP administered intrapleurally in patients with free-flowing malignant pleural effusions. Twenty-one patients were treated with escalating doses of L-NDDP by intrapleural administration over 30 min every 21 days. Fourteen patients had adenocarcinoma of the lung, 5 patients had malignant pleural mesothelioma (MPM), and 2 patients had ovarian carcinoma. The dose-limiting toxicity of L-NDDP was chest pain secondary to chemical pleuritis, which was severe in three of four patients treated at 550 mg/m2. The MTD was 450 mg/m2. At this dose, the only toxicity observed was grade 1-2 nausea and vomiting presenting 6-8 h after drug administration. Neither myelosuppression nor nephrotoxicity was observed. Loculation of residual pleural fluid with continued decrease over a period of weeks to months was observed in seven patients; in one of these patients (MPM), the pleural effusion disappeared without evidence of recurrence for 19 + months, and in six patients (three adenocarcinoma of the lung, two MPM, and one ovarian carcinoma), the pleural effusion was reduced by >50% for 5+, 10+, 18+, 8, 5+, and 2+ months. Plasma pharmacokinetic studies showed that the absorption of L-NDDP from the pleural cavity was rapid during the first 2 h, with levels becoming steady (bioavailable or free platinum) or increasing slowly (total plasma platinum) between 6 and 24 h after administration. Urinary excretion was negligible (1-3%). We conclude that: (a) the MTD of intrapleural L-NDDP is 50% higher than the MTD after i.v. administration; (b) intrapleural L-NDDP causes mild nausea and vomiting and no myelosuppression at the MTD; and (c) the absorption of L-NDDP into the systemic circulation is much slower than that of the parent compound cisplatin. Because of the favorable depot effect, lack of systemic toxicity, and control of the pleural effusion in three of five patients with MPM, a disease similar to ovarian carcinoma in that it tends to remain confined to a body cavity, a Phase II study of intrapleural L-NDDP administered in patients with MPM is in progress.
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PMID:Phase I clinical and pharmacological study of liposome-entrapped NDDP administered intrapleurally in patients with malignant pleural effusions. 981 94

Pemetrexed is an anti-metabolite that targets multiple enzymes in folate pathway. The main toxicities associated with pemetrexed are asthenia, nausea, diarrhea, myelosuppression, and rash. Few cases of pemetrexed induced cutaneous adverse event have been reported, mainly periorbital-facial edema and edema of the limbs. We report a case of pemetrexed-induced edema of the eyelid and feet in a patient with adenocarcinoma of the lung.
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PMID:Eyelid and feet edema induced by pemetrexed. 2806 20

Objectives: We aim to determine the feasibility, safety, maximally tolerated dose (MTD), recommended dose and potential anti-tumor activity of intrathecal pemetrexed (IP). Materials and Methods: Lung adenocarcinoma patients with recurrent or progressive leptomeningeal metastases (LM) after intrathecal chemotherapy were recruited. IP dose was escalated from 10 mg. A minimum of three patients and a maximum of six were enrolled in each cohort. Schedule protocol was IP twice per week for 2 weeks in induction therapy, followed by once per week for 4 weeks in consolidation therapy. Serial samples of plasma and cerebrospinal fluid (CSF) were obtained for pharmacokinetic studies. Results: Thirteen patients were enrolled between March 2017 and July 2018. EGFR driver oncogene was identified in most of the patients. Severe adverse events (AEs) were encountered in 31% (4/13) of the cases, including myelosuppression, radiculitis, and elevation of hepatic aminotransferases (EHA). Study protocol was revised due to lethal myelosuppression. Following protocol revision, vitamin B12 and folic acid supplementation was given at the beginning of treatment, and myelosuppression was well-controlled. Dose-limiting toxicities (DLT) were myelosuppression, radiculitis, and EHA. Two patients (2/2) developed dose-limiting myelosuppression at 15 mg level. One patient (1/6) experienced dose-limiting radiculitis and EHA at 10 mg level. MTD was 10 mg. Response rate was 31% (4/13) and disease control rate was 54% (7/13). The drug concentration showed a decreasing trend in serial CSF samples following each IP. After IP, the peak plasma concentration was reached at 4 h in two cases, 6 h in two cases, 9 h in one case, and 12 h in one case, respectively. Conclusion: Pemetrexed was appropriate for intrathecal administration. IP at 10 mg dose in combination with vitamin supplementation on the schedule of 1-2 times per week showed controllable toxicity and good efficacy. This regimen paves the way for subsequent clinical trial. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03101579.
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PMID:A Pilot Phase 1 Study of Intrathecal Pemetrexed for Refractory Leptomeningeal Metastases From Non-small-cell Lung Cancer. 3154 65


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