PubMed Health⌕ Search

Biomedical subjects

C G Moertel

Publications and source records attributed to C G Moertel.

At least 55 records · Page 3Linked to original sources
PubMed1990

Phase I and clinical pharmacological evaluation of pirozantrone hydrochloride (oxantrazole).

Pirozantrone hydrochloride, an anthrapyrazole analogue, was selected for clinical evaluation based on broad antitumor activity against murine tumor systems and on potentially less cardiotoxicity when compared to anthracyclines. This anthrapyrazole analogue is currently under clinical evaluation, and we now report results on a Phase I clinical trial incorporating a pharmacologically guided dose-escalation scheme. Dose escalation was designed to proceed by factors of 2 until the patient drug exposure (concentration x time) was 40% of the murine exposure at the LD10 dose (90 mg/m2). Thereafter, more moderate dose escalations were employed. The target concentration x time value (59 micrograms-min/ml) derived from preclinical pharmacology data was exceeded in all three patients at a dose of 90 mg/m2. A dose of 160 mg/m2 was found to reproducibly result in appropriate myelosuppression. This dose is recommended for further testing in Phase II studies. Nonhematological toxicities encountered in this trial were mild, the most notable being phlebitis at the infusion site. Objective responses were observed in two patients, one with metastatic breast cancer and another with metastatic melanoma. Following a 60-min infusion, pirozantrone hydrochloride plasma elimination was monoexponential, with a half-life of approximately 30 min, mean total body clearance of 1.29 liters/min/m2, and mean steady state volume of distribution of 29 liters/m2.

Adult↗
PubMed1990

A phase II trial of tamoxifen in hepatocellular carcinoma.

Because prolonged estrogen therapy can initiate hepatic adenomas, and estrogen receptors (ER) are found in 33% of hepatocellular carcinomas, a Phase II study of antiestrogen therapy was initiated in patients with hepatocellular carcinoma. Tamoxifen (20 mg twice a day) was administered to 33 patients who had biopsy proven and measurable hepatocellular carcinoma and who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. No patient had a complete or partial antitumor response; eight patients had stable disease ranging from 5 to 13 months. The median survival time for all patients was 6 months from the initiation of tamoxifen therapy. Four patients have continuing long-term survival of 18+, 22+, and 39+ months.

Adult↗
PubMed1990

A phase III trial on the therapy of advanced pancreatic carcinoma. Evaluations of the Mallinson regimen and combined 5-fluorouracil, doxorubicin, and cisplatin.

One hundred eighty-seven patients with histologically proven advanced pancreatic adenocarcinoma were randomly assigned to therapy with 5-fluorouracil (5-FU) alone, to the Mallinson regimen (combined and sequential 5-FU, cyclophosphamide, methotrexate, vincristine, and mitomycin C), or to combined 5-FU, doxorubicin, and cisplatin (FAP). Patients with both measurable and nonmeasurable disease were included and the primary study end point was survival. Among 41 patients with measurable disease, objective response rates were 7% for 5-FU alone, 21% for the Mallinson regimen, and 15% for FAP. The median interval to progression for each of the three regimens was 2.5 months. Survival curves intertwined with the median survival times for 5-FU alone and the Mallinson regimen at 4.5 months and for FAP at 3.5 months. Compared with 5-FU alone, both the Mallinson regimen and FAP produced significantly more toxicity. Neither the Mallinson regimen nor FAP can be recommended as therapy for advanced pancreatic carcinoma. Any chemotherapy for this disease should remain an experimental endeavor.

Adenocarcinoma↗
PubMed1990

A phase II study of the combination of etoposide and cisplatin in the therapy of advanced gastric cancer.

Forty-eight patients with advanced gastric cancer and measurable areas of malignant disease were treated with etoposide (130 mg/m2/day X 3 days) plus cisplatin (45 mg/m2day on days 2 and 3). Both drugs were given by constant intravenous infusion and repeated every 4 weeks. Common toxic reactions included nausea, vomiting, diarrhea, alopecia, peripheral neuropathy, leukopenia, and thrombocytopenia. Most patients experienced severe but reversible toxic reactions. In 46 evaluable patients an overall objective regression rate of 28% was obtained with a median duration of regression of 4 months. Regression rates were only modestly reduced among patients with prior chemotherapy exposure (21%). Whereas this combination of etoposide and cisplatin does not appear to offer any major advantage over other single and combination regimens in the treatment of advanced gastric cancer, it shows definite activity and its lack of cross-resistance with other commonly used agents for this disease could indicate a possible role in new combination or sequential chemotherapy approaches. As an interesting sidelight, we found that 21% of our patients had elevated human chorionic gonadotropin (HCG) levels, and among this group regression rates were higher than in HCG-negative patients. It would be of interest to extend these observations in other gastric carcinoma studies involving cisplatin regimens.

Adenocarcinoma↗
PubMed1990

Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma.

Twelve hundred ninety-six patients with resected colon cancer that either was locally invasive (Stage B2) or had regional nodal involvement (Stage C) were randomly assigned to observation or to treatment for one year with levamisole combined with fluorouracil. Patients with Stage C disease could also be randomly assigned to treatment with levamisole alone. The median follow-up time at this writing is 3 years (range, 2 to 5 1/2). Among the patients with Stage C disease, therapy with levamisole plus fluorouracil reduced the risk of cancer recurrence by 41 percent (P less than 0.0001). The overall death rate was reduced by 33 percent (P approximately 0.006). Treatment with levamisole alone had no detectable effect. The results in the patients with Stage B2 disease were equivocal and too preliminary to allow firm conclusions. Toxic effects of levamisole alone were infrequent, usually consisting of mild nausea with occasional dermatitis or leukopenia, and those of levamisole plus fluorouracil were essentially the same as those of fluorouracil alone--i.e., nausea, vomiting, stomatitis, diarrhea, dermatitis, and leukopenia. These reactions were usually not severe and did not greatly impede patients' compliance with their regimen. We conclude that adjuvant therapy with levamisole and fluorouracil should be standard treatment for Stage C colon carcinoma. Since most patients in our study were treated by community oncologists, this approach should be readily adaptable to conventional medical practice.

Adolescent↗
PubMed1990

Phase I and clinical pharmacological evaluation of a parenteral hexamethylmelamine formulation.

Hexamethylmelamine has been evaluated in single agent and combination regimen studies for many years, but only following p.o. administration. Pharmacological studies in animals and humans have shown that systematic availability of parent drug following p.o. administration is relatively low and variable due to extensive first-pass metabolism rather than due to poor absorption. Two Phase I clinical trials, with accompanying pharmacokinetic studies, have been conducted by using a parenteral formulation in which hexamethylmelamine was prepared by Intralipid 10%. The parenteral formulation was well tolerated by all patients receiving hexamethylmelamine by 1-day and by daily for 5-days schedules. Nausea and vomiting were the dose-limiting toxicities. Maximally tolerated doses on the 1-day and daily for 5-days schedules were approximately 850 mg/m2 and 630 mg/m2/day, respectively. No responses were observed in either study. Following i.v. administration of 540 mg/m2 hexamethylmelamine, plasma elimination was best described by a three-compartment open model with terminal half-life, total body clearance, and steady-state volume of distribution values of 10.4 h, 0.75 liter/min/m2 and 460 liters/m2, respectively. Twenty-four h urinary recoveries of parent drug were less than 1% for all patients. Accumulation of hexamethylmelamine during the 5-day treatment at 945 mg/m2 suggested possible saturation of parent drug elimination at that dose. Phase II studies are currently under way with the parenteral formulation of hexamethylmelamine.

Altretamine↗
PubMed1990

Adjuvant therapy for resectable colorectal carcinoma with fluorouracil administered by portal vein infusion. A study of the Mayo Clinic and the North Central Cancer Treatment Group.

We randomized 224 patients with resected Dukes' stage B2 or C colorectal cancer to either an untreated control group or to a group receiving 7 days of fluorouracil therapy (500 mg/m2 per day) by portal vein infusion. Randomization was accomplished during surgery after staging by frozen section. Only 5 (2.2%) of our 224 patients were ineligible, but an additional 10 patients assigned to portal vein infusion could not be treated because of technical problems with catheter placement. Toxic reactions were mild. There was only 1 postoperative death on each study arm. At present, the median follow-up for all patients is 5.5 years (range, 1.5 to 9.5 years). Interval to progression and survival curves essentially overlap. The same lack of treatment effect is seen in both the stage B and C subsets.

Adenocarcinoma↗
PubMed1990

Cytoreductive hepatic surgery for neuroendocrine tumors.

We retrospectively reviewed 37 patients who underwent hepatic resection between 1970 and 1989 to evaluate the role of cytoreductive hepatic surgery in patients with metastatic neuroendocrine tumors (carcinoid, 24; islet cell, 13). Seventeen resections were curative (no gross residual tumor); nine patients had symptomatic endocrinopathies and seven patients had symptoms caused by the primary tumor. Eight of nine patients with symptomatic endorcrinopathies obtained complete relief of symptoms; five are alive with no evidence of disease at 2 to 82 months (mean, 26 months). Six of seven patients with symptoms caused by the primary tumor obtained complete relief; five are alive with no evidence of disease at 5 to 28 months (mean, 14 months). One symptom-free patient underwent curative hepatic resection 5 years after abdominoperineal resection for a rectal carcinoid. Twenty resections were palliative (gross residual tumor); 16 patients had symptomatic endocrinopathies and 4 patients had symptoms caused by the primary tumor. Eight of 16 patients with symptomatic endocrinopathies obtained complete relief; five are alive at 2 to 30 months (mean, 11 months), with a mean duration of complete relief of 6 months (3 to 12 months). All four patients who underwent resection for symptoms caused by the primary tumor obtained complete relief; two are alive and symptom free at 10 and 101 months. Our experience suggests that curative surgery should be considered in all patients with completely resectable metastatic disease and that palliative surgery, despite the short duration of complete relief, should be considered in selected patients because it delays and may reduce the subsequent need for medical therapy.

Endocrine System Diseases↗
PubMed1989

Recombinant interferon-gamma lacks activity against metastatic colorectal cancer but increases serum levels of CA 19-9.

A clinical trial to determine the antitumor activity of recombinant interferon-gamma (rIFN-gamma) was conducted in 36 patients with advanced colorectal cancer. Severe constitutional symptoms were seen in the first five patients who received rIFN-gamma as a 2- to 4-hour intravenous infusion, and this method of administration was therefore abandoned. One transient partial tumor regression was observed in the 31 patients who received treatment by the intramuscular route of administration. Although a clinically tolerable regimen suitable for outpatient administration was developed, rIFN-gamma given in this dose and schedule had minimal antitumor effect for the treatment of advanced colorectal cancer. NK activity was depressed within 48 hours of rIFN-gamma administration but became significantly higher than normal controls or pretreatment levels during therapy despite disease progression, indicating discordance between augmentation of this immune parameter and tumor status. Serum CA 19-9 levels were unusually high and increased significantly more than CA 125 or CEA during rIFN-gamma treatment. This observation suggests that rIFN-gamma could augment localization of anti-CA 19-9 used to diagnostically image or therapeutically target a labeled chemotherapy agent to tumor in those patients expressing this antigen.

Adult↗
PubMed1989

Patterns of occult bleeding in asymptomatic colorectal cancer.

The assumption that asymptomatic colorectal cancers bleed provides the rationale for widespread stool screening. The authors studied 12 patients with unoperated colorectal cancer but without colorectal symptoms and six healthy volunteers as laboratory controls. All stools were collected for 2 weeks and analyzed by the HemoQuant and Hemoccult tests. In controls, the mean HemoQuant value was 0.7 mg hemoglobin (Hb)/g stool (range, 0.1-1.8) and all stools were Hemoccult-negative. In cancer patients, the mean HemoQuant was 3.3 mg Hb/g (range, 0.3-13.2); stools were within the normal HemoQuant range (less than 2 mg Hb/g) in 38% and negative by Hemoccult in 70%. The mean cancer detection rate testing a single stool per patient was 57% for HemoQuant and 25% for Hemoccult (P less than 0.001). The detection rate rose testing multiple stools and was maximal with five stools at 83% for HemoQuant compared to 31% for Hemoccult (P less than 0.001). The authors conclude that fecal blood levels are commonly normal with asymptomatic colorectal cancer. Although higher with HemoQuant than Hemoccult, cancer detection rates by fecal blood testing appear to be lower than previously reported.

Adenocarcinoma↗
PubMed1989

The physician's responsibility toward hopelessly ill patients. A second look.

Physicians have a specific responsibility toward patients who are hopelessly ill, dying, or in the end stages of an incurable disease. In a summary of current practices affecting the care of dying patients, we give particular emphasis to changes that have become commonplace since the early 1980s. Implementation of accepted policies has been deficient in certain areas, including the initiation of timely discussions with patients about dying, the solicitation and execution in advance of their directives for terminal care, the education of medical students and residents, and the formulation of institutional guidelines. The appropriate and, if necessary, aggressive use of pain-relieving substances is recommended, even when such use may result in shortened life. We emphasize the value of a sensitive approach to care--one that is adjusted continually to suit the changing needs of the patient as death approaches. Possible settings for death are reviewed, including the home, the hospital, the intensive care unit, and the nursing home. Finally, we consider the physician's response to the dying patient who is rational and desires suicide or euthanasia.

Ethics, Medical↗
PubMed1989

Biochemical modulation of fluorouracil: evidence of significant improvement of survival and quality of life in patients with advanced colorectal carcinoma.

The purpose of this study was to evaluate the effectiveness of several new approaches designed to enhance the activity of fluorouracil (5-FU) in the management of advanced colorectal cancer. A total of 429 patients were randomized to one of the following regimens: single-agent 5-FU, given by standard 5-day, intensive-course intravenous bolus technique; 5-FU plus high-dose folinic acid (leucovorin) or 5-FU plus low-dose leucovorin; 5-FU plus high-dose methotrexate (MTX) with oral leucovorin rescue; 5-FU plus low-dose MTX; and 5-FU plus cisplatin (CDDP). The median survival for patients receiving 5-FU alone was 7.7 months. The high- and low-dose leucovorin plus 5-FU regimens had median survivals of 12.2 and 12.0 months, respectively, and offered a significant survival advantage over 5-FU alone with one-sided P values of .037 and .050, respectively (P = .051 for each treatment after correction for prognostic variables). The only other regimen possibly associated with improved survival was high-dose MTX plus 5-FU, with a median survival of 10.5 months (P = .21, P = .076 corrected). In addition, both high- and low-dose leucovorin plus 5-FU regimens were associated with significantly improved tumor response rates (P = .04 and .001) and significantly improved interval-to-tumor-progression rates (P = .015 and .007) when compared with 5-FU alone. Only the low-dose leucovorin plus 5-FU regimen was associated with significant (P less than .05) superiority in each of the following parameters of quality of life: performance status, weight gain, and symptomatic relief. The overall most therapeutically favorable regimen in this trial was 5-FU given with low-dose leucovorin; fortuitously, this regimen is associated with very low drug cost. Whereas this is the first study to demonstrate both improved palliation and survival for any regimen compared with 5-FU given by rapid intravenous (IV) injection for 5 consecutive days at a dose of 500 mg/m2/d in patients with advanced colorectal cancer, the magnitude of the gain is still relatively small. Our low-dose leucovorin plus 5-FU regimen is currently being studied in a national trial with the hope that this increased advanced disease activity may produce more substantive gains in the surgical adjuvant setting.

Adenocarcinoma↗
PubMed1989

Surgical adjuvant therapy of large-bowel carcinoma: an evaluation of levamisole and the combination of levamisole and fluorouracil. The North Central Cancer Treatment Group and the Mayo Clinic.

A total of 401 eligible patients with resected stages B and C colorectal carcinoma were randomly assigned to no-further therapy or to adjuvant treatment with either levamisole alone, 150 mg/d for 3 days every 2 weeks for 1 year, or levamisole plus fluorouracil (5-FU), 450 mg/m2/d intravenously (IV) for 5 days and beginning at 28 days, 450 mg/m2 weekly for 1 year. Levamisole plus 5-FU, and to a lesser extent levamisole alone, reduced cancer recurrence in comparison with no adjuvant therapy. These differences, after correction for imbalances in prognostic variables, were only suggestive for levamisole alone (P = .05) but quite significant for levamisole plus 5-FU (P = .003). Whereas both treatment regimens were associated with overall improvements in survival, these improvements reached borderline significance only for stage C patients treated with levamisole plus 5-FU (P = .03). Therapy was clinically tolerable with either regimen and severe toxicity was uncommon. These promising results have led to a large national intergroup confirmatory trial currently in progress.

Adult↗
PubMed1989

Therapy of metastatic carcinoid tumor and the malignant carcinoid syndrome with recombinant leukocyte A interferon.

Twenty-seven patients with metastatic carcinoid tumor, 24 of whom had the malignant carcinoid syndrome, were treated with recombinant leukocyte A interferon at a planned dose of 24 x 10(6) U/m2. Twenty percent of patients with measurable tumor experienced an objective regression and 39% of those with the carcinoid syndrome experienced a reduction of more than 50% in urine 5-hydroxyindoleacetic acid (5HIAA) excretion. Flushing was partially or completely relieved in 65% of patients and diarrhea was relieved in 33%. Regrettably, these favorable treatment effects were transient in nature, with objective regressions persisting for a median of only 7 weeks and hormonal responses for a median of only 4 weeks. Any therapeutic gain experienced by these patients seemed to be outweighed by the frequency and severity of toxic reactions, which consisted primarily of chills and fever, fatigue, anorexia, weight loss, leukopenia, and abnormalities of liver function. Whereas other interferons, administration by alternative dosages and regimens, or incorporation of interferons into drug combinations may merit future study, we cannot recommend recombinant leukocyte A interferon, administered by the methods we employed, for routine therapy of the carcinoid tumor or syndrome.

Adolescent↗
PubMed1988

A phase I clinical trial of recombinant human tumor necrosis factor.

We performed a Phase I assessment of recombinant human tumor necrosis factor (rTNF-alpha) in 27 patients with advanced solid neoplasms. Therapy consisted of a 30-minute intravenous (IV) infusion on days 1 through 5, every 2 to 3 weeks. Daily doses ranged from 5 micrograms/m2 to 200 micrograms/m2. Dose-limiting sequelae were hypotension, rigors, and phlebitis. Transient fatigue and fever (median, 38 degrees C) were not clearly dose-related between 5 micrograms/m2/d and 150 micrograms/m2/d. Other reversible complications in three patients included transient leukopenia (leukocyte count, 1.3, 1.2 X 10(3)/microliters in two patients) at a dose of 5 micrograms/m2/d and 150 micrograms/m2/d, respectively; and thrombocytopenia (leukocyte count, 73 X 10(3)/microliters) at 10 micrograms/m2/d. Among 22 patients with initial and subsequent differential counts, the median number of eosinophils at the commencement of therapy was 182 cells/microliters compared with a subsequent median of 462 cells/microliters. We also detected hypertriglyceridemia in all patients. The median baseline increased from 93 mg/dl (range, 56 to 219 mg/dl) to 203 mg/dl (range, 94 to 454 mg/dl). From our experience, a clinically manageable outpatient regimen for Phase II trials consists of rTNF-alpha (150 micrograms/m2) followed by a 1-hour IV infusion of 500 ml of normal saline to abrogate hypotension daily for 5 days every 2 weeks for four cycles, then every 3 weeks thereafter to facilitate recovery from constitutional sequelae.

Adult↗