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Biomedical subjects

J B Craig

Publications and source records attributed to J B Craig.

At least 37 records · Page 2Linked to original sources
PubMed1991

Posterior atlantoaxial arthrodesis. A simplified method.

A simplified method of posterior atlantoaxial arthrodesis allowing immediate stabilization and mobilization is described. This method of fixation has been used since 1984 in 33 cases, with the indications being nonunion of odontoid peg fractures, atlantoaxial dislocation, and other traumatic conditions about the axis. A solid fusion was noted in all 33 patients by 3 months postsurgery, and the complication rate was minimal. This method of atlantoaxial arthrodesis is simple, allows immediate mobilization, controls rotation and lateral bending, and is inexpensive.

Adult↗
PubMed1990

A phase II trial of high-dose cytarabine and cisplatin in previously untreated non-small cell carcinoma of the lung. A Piedmont Oncology Association Study.

Thirty-seven chemotherapy-naive patients with advanced non-small cell lung cancer (NSCLC) were treated with cytarabine (3 g/m2 intravenously [IV] during 3 hours) after IV bolus cisplatin (100 mg/m2 repeated every 3 weeks). Aside from nausea and vomiting, the principal toxicity was hematologic, with Grade IV myelosuppression in 32% and Grade III in 14%. Four patients died while on study. One complete and four partial responses were observed for an overall response rate of 14%. Responses were limited to lymph node and lung metastases and occurred in two of 17 adenocarcinomas, two of 12 squamous cell carcinomas, and one of eight large cell carcinomas. At this dose, the plasma level of cisplatin is only 3 micrograms/ml and the plasma level of cytarabine is 10 to 50 micrograms/ml, compared with the levels of 10 micrograms/ml and 1000 micrograms/ml, respectively, required for in vitro synergy. The severity of myelotoxicity observed indicates that, even at these levels, cisplatin enhances cytarabine activity. The combination may prove useful in malignancies that are sensitive to cytarabine, but is not of benefit in cytarabine-resistant malignancies such as NSCLC.

Adult↗
PubMed1990

Vincristine infusion with CHOP-CCNU in diffuse large-cell lymphoma.

Phase I and II trials of vincristine infusion have demonstrated the safety and efficacy of this approach in the treatment of patients with refractory non-Hodgkin's lymphoma. Subsequently, a trial was designed to evaluate this technique in untreated patients. Repeated 5-day infusions of vincristine 0.25 mg/m2 per day were incorporated into a CHOP-CCNU regimen and administered to 24 patients with advanced diffuse large-cell lymphoma. Objective responses occurred rapidly and were observed in 18 (75%) patients in whom 13 (54%) were complete. Toxicity was generally mild to moderate and neurotoxicity appeared to be no worse than typically observed with bolus vincristine. Complete responses have been durable in most patients and 10 (77%) of the complete responders have not relapsed. At this time, 9 (38%) of the total patients remain alive and without evidence of disease from 3.8 to 7.3 years from the start of treatment. One patient died of disseminated gastric cancer at 3.3 years from the start of therapy and there was no evidence of lymphoma at exploratory laparotomy. Infusion of vincristine may be safely incorporated into multiagent chemotherapy programs of the CHOP type for non-Hodgkin's lymphoma. Its potential for protracted nonmyelosuppressive cell kill would appear attractive in designing future trials for this disease.

Adult↗
PubMed1990

Correlation of the proliferative index of residual leukemia with outcome in patients treated with sequential high dose ara-C and asparaginase.

Therapy of acute myelogenous leukemia (AML) with sequential high-dose ara-C and asparaginase (HiDAC----ASNase) on a day 1 and 8 schedule was designed to exploit potential recruitment of residual leukemia cells following initial cytoreduction from day 1 treatment. DNA flow cytometry was used to evaluate the proliferative index (%S + G2M) of bone marrow leukemia cells from pretreatment and day 8 marrow samples. The proliferative index on day 1, day 8, and incremental change (day 8 minus day 1) were analyzed for their correlation with bone marrow aplasia on day 15 and with the attainment of subsequent complete remission. Pretreatment (day 1) and the change in proliferative index did not correlate (p greater than 0.10) with day 15 marrow aplasia or with clinical outcome. However, the magnitude of the day 8 proliferative index did relate to the attainment of bone marrow aplasia on day 15 (p = 0.05) and the attainment of complete remission (p = 0.002). Recruitment of residual leukemia cells into the proliferative phases of the cell cycle may contribute to the unique efficacy of the day 1 and 8 schedule of HIDAC----ASNase. Additionally, the cytokinetics of residual leukemia after initial chemotherapy may be predictive of outcome and could be useful as a marker for the design of optimal therapeutic regimens.

Adolescent↗
PubMed1989

Phase II trial of a new biological response modifier (ImuVert) in advanced prostate cancer.

ImuVert, a new biological response modifier of bacterial origin, was evaluated in a Phase II trial of patients with metastatic prostate cancer. Sixteen patients with hormone refractory measurable or evaluable disease were treated with ImuVert 1.0 mg subcutaneously once weekly for 5 weeks. After a 1 week rest period, the dose was escalated to 3.0 mg weekly for 5 additional weeks. Eleven patients received the full 10 weeks of therapy. Toxicity consisted of mild transient flu-like symptoms as well as the development of tenderness and induration at injection sites. No patient responded to treatment. ImuVert at this dose and schedule is inactive in advanced prostate cancer.

Aged↗
PubMed1989

Phase I clinical investigation of amonafide.

Amonafide (benzisoquinolinedione, NSC 308847) is a new synthetic imide antineoplastic agent with DNA intercalative properties that has been evaluated in a phase I clinical trial. The drug was administered as a single intravenous (IV) infusion over 30 to 120 minutes repeated every 28 days. Ninety-five courses of therapy at doses ranging from 18 to 1,104 mg/m2 were administered to 38 patients with refractory solid tumors. Granulocytopenia was dose limiting. Leukopenia was seen in 13 of 31 courses at doses of 690 mg/m2 or greater. Life-threatening granulocytopenia (less than or equal to 250 microliters) was noted in 1/6 patients treated at 800 mg/m2, 1/8 patients treated at 918 mg/m2, and 2/5 patients treated at 1,104 mg/m2. No definite relationship between myelotoxicity and prior treatment status was noted. Rate-of-infusion dependent, nonhematologic toxicities included diaphoresis, flushing, dizziness, and tinnitus, all of which were ameliorated by increasing the duration of drug infusion to 120 minutes. In addition, nausea and vomiting (grades 1 and 2) were seen in 29/56 courses at doses greater than or equal to 519 mg/m2, but were easily controlled by phenothiazine antiemetics. Amonafide plasma and urine concentrations were determined by high-pressure liquid chromatography (HPLC). Plasma concentrations declined biexponetially with a terminal harmonic mean terminal half-life (t 1/2) of 5.5 h. The mean apparent volume of distribution at steady-state and total body clearance were 532 L/m2 and 84 L/h/m2, respectively. Less than 5% of the total dose of amonafide was excreted unchanged in the urine. Antitumor activity has been noted in one patient with non-small-cell lung cancer (one complete response exceeding 29 months duration) and in one patient with prostatic cancer (complete pain relief and improvement in bone scan for 9 months). The recommended dose for phase II trials with this schedule of amonafide is 918 mg/m2 with dose escalation to amonafide is 918 mg/m2 with dose escalation to myelotoxicity.

Adenine↗
PubMed1988

Phase I clinical trial of carbetimer.

Carbetimer (carbethimer, N-137, NED-137, carboxyimamidate) is a low molecular weight polyelectrolyte with antitumor activity in a variety of tumor models. This phase I trial evaluated a single dose of carbetimer infused over 1-2 h every 28 days. Forty-three patients received 71 courses of the drug at doses ranging from 180 to 8500 mg/m2. The dose-limiting toxicity was hypercalcemia (serum calcium greater than 12.5 mg/dl) noted in two of three patients at a dose of 8500 mg/m2. Serum calcium levels between 10.5 and 12.5 mg/dl were noted in an additional three patients treated at doses greater than or equal to 1600 mg/m2. Calcium balance studies in three patients treated at 6500 mg/m2 revealed an increase in urinary cyclic AMP and phosphate excretion after treatment accompanied by a mild elevation of serum parathyroid hormone. Immunological studies in these patients revealed a statistically significant increase in the percentage of peripheral T-helper cells. An increase in the T-helper/suppressor cell ratio was observed in two of the three patients studied. Interleukin 2 production by phytohemagglutinin-stimulated peripheral mononuclear cells was increased in two of three patients. One patient with a renal cell carcinoma showed a mixed response. The recommended dose for phase II trials as assessed from this study is 6500 mg/m2 as a single dose every 28 days.

Adult↗
PubMed1988

Phase I and clinical pharmacology trial of crisnatol (BWA770U mesylate) using a monthly single-dose schedule.

Crisnatol is a novel lipophilic arylmethylaminopropanediol with significant antineoplastic activity in a variety of murine and human tumor models which functions as a DNA intercalator. In this Phase I trial, a 6-h infusion of the drug was administered i.v. in 700 to 1500 ml of 5% dextrose in water every 28 days. Eighty-five courses at doses of 7.5 to 516 mg/m2 were administered to 43 patients with refractory solid tumors. Reversible neurological toxicity was dose limiting at 516 mg/m2 and was manifested as somnolence, dizziness, blurred vision, unsteady gait, and alpha-slowing on electroencephalogram at the end of infusion. All neurological signs and symptoms were reversible. No hematological toxicity was observed. Other toxicities included phlebitis, mild to moderate nausea and vomiting, reversible sinus node arrest in one patient, and hypertension. Crisnatol plasma concentrations were determined by high-pressure liquid chromatography. After infusion, plasma concentrations declined biexponentially with a terminal t1/2 of 2.9 h. Using a two-compartment model, the mean apparent volume of distribution at steady state and total-body clearance were 58.8 liters/m2 and 18.3 liters/h/m2, respectively, indicative of extensive tissue distribution and rapid hepatic clearance. Peak plasma levels occurred at the end of infusion and correlated with the onset of neurological toxicity. The recommended Phase II dose for this schedule is 388 mg/m2.

Adult↗
PubMed1988

Tumor necrosis factor not detectable in patients with clinical cancer cachexia.

Tumor necrosis factor (TNF) has been implicated in the pathogenesis of cachexia in neoplastic and infectious diseases. To assess the relationship between TNF and weight loss among cancer patients, we assayed TNF levels in serum from 19 patients who had lost 8%-40% of premorbid weight. The weight loss experienced by these patients was not attributable to anticancer therapy, gastrointestinal disorders, or other medical problems. TNF was measured using a quantitative sandwich enzyme-linked immunosorbent assay that is sensitive to human TNF in serum at concentrations greater than or equal to 40 pg/mL. No TNF was detected in serum samples from the 19 patients studied.

Adult↗
PubMed1988

Phase I-II trial of acivicin in adult acute leukemia.

Six patients with relapsed or refractory acute leukemia were treated with 9 mg/m2 or 11 mg/m2 of acivicin daily for seven days in a phase I-II trial. No responses were attained and further dose escalation was prohibited by neurotoxicity in 2 of 3 patients who received 11 mg/m2/day. Although acivicin appears to have limited potential as a single agent, laboratory evaluation of leukemic blasts in one patient revealed cell cycle (S-phase accumulation) and metabolic effects which suggest that acivicin may be effective as a modulator of other antileukemia agents such as cytosine arabinoside.

Aged↗
PubMed1988

Phase II trial of high-dose cytosine arabinoside and cisplatin in recurrent squamous carcinoma of the head and neck. A Piedmont Oncology Association Study.

Fifteen patients with recurrent squamous carcinoma of the head and neck received high-dose cytosine arabinoside (ara-C) (3 g/m2) and cisplatin (100 mg/m2) every 3 weeks in an attempt to explore the dose-dependent synergy between these two agents. A partial response was attained in one patient; there were no complete responses. The major toxicity was myelosuppression. With the current schedule, high-dose ara-C failed to improve the response rate achieved with cisplatin alone.

Adult↗
PubMed1987

Phase I study of high-dose cytosine arabinoside and etoposide in patients with advanced malignancies.

Cytosine arabinoside (ara-C) and etoposide (VP-16) display synergy in the laboratory. Twenty-six patients participated in a phase I study of high-dose ara-C in combination with VP-16. The dose of VP-16 was held constant at 50 mg/m2 as an intermittent infusion over 33 h; escalating doses of ara-C were given as infusions during hours 9-12 and 21-24. Myelosuppression was the dose-limiting toxicity and occurred with doses considerably less than those expected from studies of the two drugs as single agents. The suggested initial doses for phase II trials with this schedule are 750 mg/m2 X 2 doses of ara-C and 50 mg/m2 of VP-16. Nonhematologic toxicity was minimal; therefore, further dose escalation is feasible in patients in whom myelosuppression is acceptable.

Adult↗
PubMed1987

Treatment of advanced colorectal carcinoma with actinomycin D, vincristine, methyl-CCNU, and methotrexate.

Twenty patients with advanced colorectal carcinoma were treated with combination chemotherapy consisting of actinomycin D, vincristine, methyl-CCNU, and methotrexate. Fourteen patients had received prior chemotherapy with 5-fluorouracil (5-FU). No complete responses and only one partial response were observed for an overall response rate of 5%. The combination of actinomycin D, vincristine, methyl-CCNU, and methotrexate at the doses and schedule used was of no value in the treatment of patients with metastatic colorectal carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

The management of nausea and vomiting in clinical oncology.

The development of cisplatin and the use of intensive combination chemotherapy have resulted in significant therapeutic advances in medical oncology, as well as the need for intensive supportive care aimed at ameliorating enhanced toxicity. From the patient's perspective, the most prominent adverse effects of chemotherapy are nausea and vomiting. Inadequate control of these symptoms leads to physiologic debilitation and psychologic distress, sequelae that result in either the patient being medically unable to continue therapy or noncompliant. Recent antiemetic research has created a voluminous data base from which the appropriate management of many aspects of chemotherapy-induced emesis can be gleaned. Despite these advances, at least 30% of patients continue to experience some degree of acute emesis with chemotherapy, and the problems of delayed and anticipatory nausea and vomiting have just begun to be addressed. Effective management of chemotherapy-induced emesis is an important aspect of the total care of oncologic patients, improving patient compliance and enhancing the therapeutic index of chemotherapy regimens resulting in a decrease in the overall morbidity and mortality of cancer therapy.

Antiemetics↗
PubMed1987

Adjuvant chemotherapy of solid tumors.

Adjuvant chemotherapy for microscopic disease following eradication of clinically detectable lesions by primary surgery and/or radiotherapy is of documented benefit for some oncology patients. However, for many primary cancers efficacy is limited to specific subgroups of patients or has demonstrated no advantage over primary therapy alone. The rationale for adjuvant chemotherapy and results of selected trials are reviewed. In patients for whom adjuvant therapy is of demonstrated benefit, further trials aimed at delineation of patient selection factors, optimal chemotherapy regimens and schedules, and duration of therapy are needed; progress in adjuvant treatment of other subgroups may require development of more effective antineoplastic drugs, in addition to exploration of these factors.

Breast Neoplasms↗
PubMed1987

Antiemetic therapy in patients treated with high-dose cytosine arabinoside.

The antiemetic efficacy of metoclopramide (MCP) was evaluated in 33 consecutive patients treated with high-dose cytosine arabinoside (HiDAC), greater than or equal to 3 g/m2, a highly emetogenic agent increasingly used in patients with hematologic malignancies for which no previous formal antiemetic trials have been reported. Administration of MCP in conjunction with prophylactic diphenhydramine resulted in major antiemetic responses (0-2 episodes of emesis in the 24 h after therapy) in 23 of 33 (70%) patients. The addition of lorazepam (LZP) to MCP resulted in major antiemetic response in 7 or 8 (88%) patients who failed to respond to MCP alone. Major side effects were extrapyramidal reactions (5%) and moderate diarrhea (18%). MCP alone or in conjunction with LZP is effective antiemetic therapy in patients treated with HiDAC.

Adolescent↗