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Biomedical subjects

C G Kardinal

Publications and source records attributed to C G Kardinal.

At least 37 records · Page 2Linked to original sources
PubMed1994

Randomized comparison of two schedules of fluorouracil and leucovorin in the treatment of advanced colorectal cancer.

PURPOSE: To compare two commonly used schedules of fluorouracil (5FU) and leucovorin in the treatment of patients with advanced metastatic colorectal cancer. Each of these dosage administration schedules has been demonstrated to be superior to single-agent bolus 5FU in previous controlled trials. PATIENTS AND METHODS: Three hundred seventy-two ambulatory patients with metastatic colorectal cancer were stratified according to performance status, and presence and location of any measurable indicator lesion(s). They were then randomized to receive chemotherapy with one of the following regimens: (1) intensive-course 5FU plus low-dose leucovorin (5FU 425 mg/m2 plus leucovorin 20 mg/m2 intravenous [IV] push daily for 5 days with courses repeated at 4- to 5-week intervals); (2) weekly 5FU plus high-dose leucovorin (5FU 600 mg/m2 IV push plus leucovorin 500 mg/m2 as a 2-hour infusion weekly for 6 weeks with courses repeated every 8 weeks). RESULTS: Three hundred sixty-two of 372 patients randomized (97.3%) were eligible and included in the analysis. Three hundred forty-six patients (95.6%) have died. There were no significant differences in therapeutic efficacy between the two 5FU/leucovorin regimens tested with respect to the following parameters: objective tumor response (35% v 31%), survival (median, 9.3 v 10.7 months), and palliative effects (as assessed by relief of symptoms, improved performance status, and weight gain). There were significant (P < .05) differences in toxicity, with more leukopenia and stomatitis seen with the intensive-course regimen, and more diarrhea and requirement for hospitalization to manage toxicity with the weekly regimen. Financial cost was also higher with the weekly regimen. CONCLUSION: Intensive-course 5FU plus low-dose leucovorin appears to have a superior therapeutic index compared with weekly 5FU plus high-dose leucovorin using the dosage administration schedules applied in this study based on similar therapeutic effectiveness, but lower financial cost, and less need for hospitalization to manage chemotherapy toxicity.

Aged↗
PubMed1994

Sequencing and schedule effects of cisplatin plus etoposide in small-cell lung cancer: results of a North Central Cancer Treatment Group randomized clinical trial.

PURPOSE: The combination of etoposide (E) and cisplatin (P) is an accepted standard therapy for small-cell lung cancer (SCLC); however, the optimal sequencing and administration schedule has not been defined. This study was designed to evaluate different sequencing and administration schedules of E and P in the treatment of SCLC. PATIENTS AND METHODS: Five hundred fifty-two eligible patients with limited-(LD) and extensive-stage (ED) SCLC were randomized to receive one of the following regimens: arm A, P 30 mg/m2 by intravenous (IV) bolus followed by E 130 mg/m2 bolus; arm B, E 130 mg/m2 bolus followed by P 30 mg/m2 bolus; arm C, E 130 mg/m2 by 24-hour infusion and P 30 mg/m2 bolus at the end of each 24-hour infusion of E; arm D, E 130 mg/m2 by 24-hour infusion and P 45 mg/m2 by 24-hour infusion on day 2 and 3 only. Two 3-day induction cycles of IV EP were administered 4 weeks apart. Subsequent therapy was the same for all arms, consisting of four cycles of cyclophosphamide, doxorubicin, and vincristine (CAV) at 4-week intervals. Consolidative thoracic radiation therapy (TRT) and prophylactic cranial irradiation (PCI) were administered to responders. RESULTS: The overall response rate (84%) was similar in all treatment arms. Treatment arm A was associated with the best complete response (CR) rate (52%), the most favorable median survival time (MST) of 15 months, and a 26% 2-year survival rate. Patients with LD on arm A had a MST of 20 months and a 42% 2-year survival rate. Multivariate analysis indicated that extent of disease, performance status, arm of therapy, and sex were significant independent factors influencing survival. Toxicity of the four regimens was similar, except for greater thrombocytopenia on arm D. CONCLUSION: The bolus administration of EP with E following P for the first two cycles of chemotherapy was the most effective regimen, with especially encouraging survival for LD patients.

Actuarial Analysis↗
PubMed1994

Phase III trial of recombinant interferon gamma in complete responders with small-cell lung cancer.

PURPOSE: We evaluated the effect of recombinant interferon gamma (rIFN-gamma) on survival and toxicity in small-cell lung cancer (SCLC) patients in complete remission (CR). PATIENTS AND METHODS: One hundred patients in CR following treatment with six cycles of combination chemotherapy, thoracic radiotherapy (TRT), and prophylactic cranial irradiation (PCI) were studied. All patients had been enrolled onto a cooperative group trial (North Central Cancer Treatment Group [NCCTG] 86-20-51). Patients received observation only or rIFN-gamma at a dose of 4 x 10(6) U subcutaneously per day for 6 months. RESULTS: Six patients (12%) did not comply with rIFN-gamma treatment. Substantial nonhematologic toxicities consisting of chills, myalgia, lethargy, and alteration of mood-personality were observed. No patient experienced life-threatening or fatal toxicity. The median times to progression for rIFN-gamma treatment or observation were 6.9 and 8.1 months (P = .54). The median survival times were 13.3 and 18.8 months, respectively (P = .43). Approximately 70% of all patients relapsed within 2 years. CONCLUSION: Time to progression and survival were inferior in patients treated with rIFN-gamma compared with randomized control subjects, although this difference was not statistically significant. These data indicate that rIFN-gamma treatment is not associated with a 33% improvement in survival (P = .04). Because of the high rate of relapse, SCLC patients in CR are an ideal group in which to evaluate novel and minimally toxic agents.

Adult↗
PubMed1994

Ethical issues in cancer clinical trials.

Prospective randomized trial is the gold standard in clinical research. Randomized trials tend to reduce and even eliminate investigator and patient bias. A poorly-designed or improperly randomized study involving human subjects that will not or cannot answer a scientific question is by definition unethical. However, a well-designed clinical trial is not inherently ethical. Physicians involved in a randomized trial must make the intellectually honest admission that the best therapy for the individual's disease is not yet known. The ultimate protection for human subjects who volunteer to participate in clinical trials is the responsible investigator himself. In patients with advanced cancer there are three primary factors motivating participation: hope that the new treatment will offer a better chance for controlling disease; altruism that even if the treatment did not help them as an individual it might ultimately help others; and trust that the physician would not recommend that the patient enter investigational therapy unless he thought it might be helpful.

Ethics, Medical↗
PubMed1993

Combined doxorubicin and alpha-interferon therapy of advanced hepatocellular carcinoma.

BACKGROUND: Modest activity for doxorubicin has been detected repeatedly for the therapy of advanced hepatocellular carcinoma. Variable activity in this disease also has been documented for alpha-interferon. Preclinical data indicated the possibility that alpha-interferon could enhance or add to the cytotoxic effect of doxorubicin. METHODS: The authors evaluated the use of alpha-interferon at a dose of 12 x 10(6) units/m2/day for 5 days given by intramuscular injection plus doxorubicin 25-40 mg/m2 given intravenously on day 3 (both repeated every 4 weeks) for the treatment of advanced hepatocellular carcinoma. RESULTS: Among 31 eligible patients treated, there was only one instance of objective tumor regression. The median survival for all patients was 10 months. Both hematologic and nonhematologic toxicity were significant but tolerable to the patients. CONCLUSIONS: The 3% response rate indicated that, by the method used, the addition of alpha-interferon to doxorubicin does not improve the clinical effectiveness. This combination cannot be recommended for further study.

Adult↗
PubMed1993

Breast Cancer Prevention Trial update.

In April 1992, the National Surgical Adjuvant Breast and Bowel Project and the National Cancer Institute launched the Breast Cancer Prevention Trial. This is the largest cancer prevention trial ever attempted. The Breast Cancer Prevention Trial will involve 16,000 high-risk women in the United States and Canada. Half will receive tamoxifen and half placebo. Currently, over 5,000 women have been enrolled in the Breast Cancer Prevention Trial. The Ochsner Community Clinical Oncology Program in New Orleans is coordinating the trial in Louisiana and Mississippi. Other participating centers in this area are located in Baton Rouge, Houma, and New Orleans East in Louisiana, and Biloxi, Gulfport, Hattiesburg, and Jackson in Mississippi.

Adult↗
PubMed1993

Is breast preservation possible in women with large, locally advanced breast cancers?

Breast conservation therapy is an accepted treatment option for early stage breast carcinoma, but is rarely considered appropriate for locally advanced nonmetastatic lesions. Mastectomy specimens of 46/50 patients treated at the Ochsner Clinic and the Mallinckrodt Institute of Radiology with neoadjuvant chemotherapy prior to mastectomy +/- irradiation were evaluated by a single pathologist to assess tumor response to chemotherapy. Forty percent of this group would potentially have been eligible for breast conservation therapy, using a residual tumor size of < or = 4 cm with negative surgical margins as the criteria. Patients most likely to qualify for breast conservation therapy were those with T3N0-1 lesions (67%). Least likely were patients with skin involvement at diagnosis 4/33 (12%). Tumors with an extensive intraductal component at biopsy often had residual islands of intraductal carcinoma occupying the original tumor volume, even when the invasive component was absent or much reduced. A prospective trial will be required to determine whether or not acceptable local control rates can be obtained after breast conservation therapy for that subset of patients with a favorable response to induction chemotherapy.

Adult↗
PubMed1993

Cancer chemotherapy in historical perspective.

Effective systemic cancer therapy has evolved during the past 50 years. Prior to that time a variety of treatments were attempted, many of which seemed to have had their origins in sorcery rather than science. The 1950s and 1960s produced an explosion of knowledge and many of the chemotherapeutic agents in use today were synthesized during that time frame. Currently we are exploring a variety of new therapeutic approaches to cancer, and the future promises to be increasingly productive.

Antineoplastic Agents↗
PubMed1992

A phase III trial of mitomycin C alone versus mitomycin C, vinblastine, and cisplatin for metastatic squamous cell lung carcinoma.

BACKGROUND: In an effort to confirm the efficacy of mitomycin C against metastatic squamous cell lung carcinoma and to compare the efficacy of single-agent therapy with a combination containing cisplatin, the authors conducted a randomized Phase III trial of mitomycin C alone versus mitomycin C, vinblastine, and cisplatin (MVP). METHODS: All patients had advanced squamous cell lung carcinoma, and survival was the primary end point. There were 133 eligible patients who received either mitomycin C alone (n = 64) or MVP (n = 69). The two groups were similar with respect to performance score, disease status, age, sex, and stage. RESULTS: The major objective response rates were 30% (95% confidence interval [CI], 18-41%) and 43% (95% CI, 32-55%) for mitomycin C alone and MVP, respectively (P = 0.1). The median time to progression was 83 days for mitomycin C alone, compared with 119 days for MVP (P = 0.026). The median survival time was 114 days for mitomycin C and 163 days for MVP (P = 0.09). The 1-year survival rates were equivalent. Myelosuppression was the major toxicity, and there were significantly greater leukocyte nadirs with MVP therapy (P < 0.001). CONCLUSION: Mitomycin C has antitumor activity against squamous cell lung carcinoma when used alone or in combination with MVP. The regimen containing cisplatin had marginally increased activity that did not translate into a clinically significant survival advantage.

Adult↗
PubMed1992

Improvement in 'stat' laboratory turnaround time. A model continuous quality improvement project.

BACKGROUND: Continuous quality improvement is being advocated as the process that, if adopted, would improve the efficiency, productiveness, and quality of medical institutions, thereby helping to solve the health care crisis our country is facing. To determine if these techniques could be effective in a tertiary-care multispecialty group practice, a model project was undertaken. The model project chosen was to determine if we could improve the turnaround time for "stat" laboratory examinations performed in our large outpatient facility. METHODS: A 10-member team consisting of everyone involved in the process of laboratory testing was empowered to evaluate the present process and make appropriate changes. With traditional techniques of quality improvement, the process was assessed, data were collected and statistically analyzed, changes were introduced, and data were recollected and analyzed. RESULTS: After intervention, the preanalytic delays were reduced by 76% and the postanalytic delays by 88%. Waiting time for patients was reduced by an average of 62%. By instituting the changes suggested, the institution saved $225,000 on a one-time basis and $40,000 to $50,000 on a recurring basis. CONCLUSION: Adoption of quality improvement techniques appears to be a desirable management paradigm that should be explored by all medical institutions interested in maximizing the quality of care offered while at the same time minimizing its cost.

Ambulatory Care Facilities↗
PubMed1991

Phase II trial of recombinant leukocyte A interferon (IFN-alpha 2A) plus 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and the combination cimetidine with BCNU in patients with disseminated malignant melanoma.

Sixty-two patients with biopsy-proven, measurable disseminated malignant melanoma received either the combination IFN-alpha 2A with BCNU (30 patients) or the combination cimetidine with BCNU (32 patients) in parallel noncomparative Phase II trials. From patients receiving IFN-alpha 2A plus BCNU, we observed a 7% response rate: 1 complete response (CR) and 1 partial response (PR) (soft tissue disease with durations of 6.9 and 11.5+ months, respectively). Median time to progression (MTP) was 1.8 months and median survival time (MST) was 3.8 months. Myelosuppression and a flu-type illness were the most common toxicities. From patients receiving cimetidine plus BCNU, the response rate was 16%: 4 PRs (soft tissue disease, 3.8 months; visceral, 2.1, 4.0+, and 9.7 months) and 1 CR (soft tissue, 14.3+ months). MTP and MST were 1.9 and 5.5 months, respectively. Myelosuppression and nausea/vomiting were the most common side effects. Although each of these regimens had great conceptual allure, neither offered any durable impact on the natural history of disseminated malignant melanoma. Nevertheless, alternative combinations of biological response modifiers (BRMs) and BRMs with biochemical modulators or cytotoxic agents may provide some useful alternatives for further clinical investigations.

Adult↗
PubMed1991

Biochemical modulation of fluorouracil with leucovorin: confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer.

In a previous study (J Clin Oncol 7:1407-1417, 1989), we identified two dosage administration schedules of fluorouracil (5FU) combined with leucovorin that were superior to single-agent 5FU for the treatment of advanced colorectal cancer. In this same study, a regimen of 5FU plus high-dose methotrexate (MTX) demonstrated a suggestive advantage over 5FU alone. To permit a more definitive comparison, we have extended our evaluation of these three regimens to involve an additional 259 patients. In all, 457 patients with advanced colorectal cancer were randomly assigned to one of the following regimens: 5FU plus low-dose leucovorin, 5FU plus high-dose leucovorin, or 5FU plus high-dose MTX with leucovorin rescue. We have found that each of the 5FU/leucovorin regimens demonstrates a significant (P less than or equal to .01) advantage over 5FU plus high-dose MTX for objective tumor response and interval to tumor progression. Moreover, 5FU plus low-dose leucovorin confers a significant survival benefit (P less than or equal to .01) compared with 5FU plus high-dose MTX. The 5FU plus high-dose leucovorin regimen shows a survival benefit only in unadjusted analyses (P = .04), but this difference is not significant when adjusted for imbalances in prognostic variables (P = .44). Evaluation of the two 5FU/leucovorin regimens rules out a 10% decrease in death rate for the high-dose leucovorin regimen compared with the low-dose leucovorin regimen (P less than .05). The regimen of 5FU plus low-dose leucovorin has now been shown to offer a statistically significant survival advantage versus 5FU alone and versus 5FU plus high-dose MTX, a regimen that had shown promise in earlier trials. These data confirm the efficacy of leucovorin combined with 5FU in patients with advanced colorectal cancer and establish that it is not necessary to use high doses of leucovorin to achieve these results.

Aged↗
PubMed1991

Clinical cancer research in Louisiana.

The Ochsner Medical Institutions of New Orleans and Baton Rouge, the Louisiana State Medical Centers in New Orleans and Shreveport, and the Tulane Medical Center of New Orleans are all actively involved in the conduct of National Cancer Institute approved and sponsored clinical trials. Through the efforts of investigators at these institutions, avant-garde, state-of-the-art cancer clinical trials are being made available to the citizens of the state of Louisiana.

Clinical Trials as Topic↗
PubMed1990

A controlled trial of cyproheptadine in cancer patients with anorexia and/or cachexia.

Anorexia, cachexia, and resultant weight loss are major clinical problems in a substantial proportion of patients with advanced cancer. Effective means of alleviating these problematic symptoms are lacking. Extensive clinical data demonstrate a weight enhancing effect for the serotonin antagonist, cyproheptadine, in several clinical situations. In addition, sound basic research suggests that cyproheptadine may be helpful in patients with cancer anorexia/cachexia. Because of this, the authors performed a randomized, placebo-controlled, double-blinded clinical trial using cyproheptadine, 8 mg orally three times a day in 295 patients with advanced malignant disease. Patients assigned to cyproheptadine had less nausea (P = 0.02), less emesis (P = 0.11), more sedation (P = 0.07), and more dizziness (P = 0.01) than placebo patients. Patients' appetites, measured by serial patient-completed questionnaires, appeared to be mildly enhanced by cyproheptadine. Unfortunately, cyproheptadine did not significantly abate progressive weight loss in these patients with advanced malignant disease; patients assigned to cyproheptadine lost an average of 4.5 pounds per month compared to 4.9 pounds per month for patients assigned to a placebo (P = 0.72).

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

Evaluation of the continuous infusion of etoposide plus cisplatin in metastatic breast cancer. A collaborative North Central Cancer Treatment Group/Mayo Clinic phase II study.

A prospective clinical trial was done to evaluate the efficacy and toxicity of cisplatin plus etoposide (VP-16) in patients with breast cancer who failed one previous chemotherapy regimen for advanced disease or relapsed within 12 months of adjuvant chemotherapy. Partial responses occurred in 11 of 44 evaluable patients (25%; 95% confidence interval (CI), 13% to 40%). The median time to disease progression in responding patients was 4 months (range, 3 to 6+ months), whereas the median time to disease progression and survival for all patients who were treated were 3 and 7 months, respectively. There was marked toxicity related to this protocol treatment including pancytopenia, gastrointestinal upset, and renal insufficiency. Two treatment-related deaths occurred; one from sepsis and one from renal failure. Thus, this regimen, as second-line chemotherapy for women with metastatic breast cancer, resulted in moderate, short-term, antitumor activity at the expense of marked toxicity.

Acute Kidney Injury↗