Search PubMed⌕ Search

Biomedical subjects

J Goldie

Publications and source records attributed to J Goldie.

28 records · Page 2Linked to original sources

Drug dosage intensity--a panel discussion.

There is now widespread interest in the subject of drug dose intensity in cancer treatment. Recent retrospective analyses have shown a clear-cut benefit for those patients receiving either the intended drug dosage in a particular regimen or the highest dosage achievable through an escalation scheme. In this discussion, the participating physicians will review dose intensity in light of these retrospective studies, highlighting the particular tumor types in which benefits have been demonstrated. Other important issues will be discussed, such as scheduling of drug combinations and the importance of using toxicity as a biologic response monitor of drug efficacy. The panelists will also provide opinions as to the best design for a prospective clinical trial to test dose intensity.

Antineoplastic Agents↗

Alternating chemotherapy and thoracic radiotherapy with concurrent cisplatin-etoposide for limited-stage small-cell carcinoma of the lung.

Seventy patients with limited-stage small-cell lung cancer (SCLC) were given six courses of chemotherapy alternating two drug combinations: a combination of cyclophosphamide, doxorubicin (Adriamycin [Adria Laboratories, Columbus OH]) and vincristine (CAV) was alternated with cisplatin and etoposide at 3-week intervals. Thoracic radiotherapy was administered concurrently with the first cisplatin-etoposide chemotherapy. Prophylactic cranial irradiation (PCI) was administered after the completion of all chemotherapy. No maintenance treatment was used. Seventy-six percent of patients achieved a complete clinical response. The median survival was 78 weeks and the 2-year survival rate was 32% with an average follow-up of 3 1/2 years. Seventeen percent are currently alive and disease free. Cisplatin and etoposide can be administered concurrently with thoracic irradiation with acceptable toxicity. Our results justify further clinical research using alternating chemotherapy and concurrent thoracic irradiation and cisplatin-etoposide chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

Neoadjuvant (preoperative) chemotherapy for breast cancer.

Despite recent developments in the treatment of breast cancer, metastatic breast cancer remains an incurable disease. Postoperative adjuvant treatment may improve the survival of a subgroup of node positive, Stage II breast cancer patients, but the proportion of failures is still high. Preoperative adjuvant chemotherapy, an example of a new approach in scheduling of available agents, is based on sound theoretical and experimental principles. In this report, the authors summarize the background data on the rationale for preoperative adjuvant chemotherapy and present preliminary results of this study in which preoperative treatment starting with one course of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) was given to newly diagnosed patients with breast cancer. Analysis of the first 43 patients given such treatment has shown that the side effects were comparable to those seen in patients treated with conventional postoperative chemotherapy, and that the delay time between diagnosis and starting chemotherapy has been substantially reduced compared to the historic group of patients. Additional aspects of this study include the introduction of fine-needle aspiration as the only diagnostic method for obtaining the tissue diagnosis of breast cancer, as well as a more intensive interaction between the surgeons from private practice and the oncology institute.

Adult↗

Cyclic alternating chemotherapy for small cell carcinoma of the lung.

Eighty-two previously untreated patients with small cell cancer of the lung were treated with six cycles of two alternating drug regimens: a new combination of mitomycin, methotrexate, and etoposide; and cyclophosphamide, doxorubicin, and vincristine. No maintenance chemotherapy was used. Consolidative thoracic irradiation and prophylactic cranial irradiation were employed. The median survival time for 32 limited-disease patients was 59 weeks, and for 50 extensive-disease patients was 35 weeks. Four-year survival was 12% for limited-disease patients and 2% for extensive-disease patients. These results were not superior to conventional combination chemotherapy regimens.

Adult↗

5-FU infusion in advanced colorectal cancer: a comparison of three dose schedules.

Ninety-four patients with advanced colorectal adenocarcinoma were treated by continuous iv 5-FU infusion on three different dose schedules. Thirty-three patients received a 72-hour infusion of 5-FU (30 mg/kg/24 hours) every 3 weeks (Group A); 31 received a 72-hour infusion of 5-FU (30 mg/kg/24 hours) every 2 weeks (Group B); and 30 received a 48-hour infusion of 5-FU (30 mg/kg/24 hours) every week (Group C). Although this was a sequential nonrandomized study of the dose schedules, the groups were comparable with respect to various prognostic factors. Response rates were as follows: Group A--three patients had minor response (9%) and 30 had no response (91%); Group B--five patients achieved partial response (16%), nine had minor response (29%), and 17 had no response (55%), and Group C--one patient achieved complete response (3%), eight achieved partial response (27%), five had minor response (17%), and 16 had no response (53%). The median survival time for Group A was 9 months, for Group B was 9.5 months, and for Group C was 14 months. Intensifying the dose schedule of 5-FU by increasing the frequency of administration has significantly improved response rates. A prolongation of the median survival time of patients treated with a 48-hour infusion at 1-week intervals was noted, although this was not statistically significant.

Adenocarcinoma↗

Modulation of doxorubicin resistance in P388/ADR cells by Ro44-5912, a tiapamil derivative.

We describe here investigations into the ability of a tiapamil derivative, Ro44-5912 to overcome multidrug resistance (MDR) in doxorubicin (ADR)-resistant murine leukemic P388 cells. This compound has the formula: C27H39NO4S2.1:2C6H8O6, a M. W. of 858 and is structurally similar to verapamil, an established inhibitor of P-glycoprotein (PGP). We have compared the MDR modulating properties of Ro44-5912 with verapamil in P388ADR cells. Doxorubicin concentration required to achieve 50% inhibition of growth (IC50) for P388ADR cells was found to be 24 microM. In contrast, treatment of P388ADR cells with Doxorubicin and 3 microM verapamil decreased the IC50 value to 2.5 microM. A further decrease was observed with 3 microM Ro44-5912 treatment, where an IC50 value of 1.1 microM was obtained. Doxorubicin accumulation was also determined by flow cytometry in order to determine whether the increased levels of chemosensitivity observed for Ro44-5912 were reflected by increased cellular drug uptake. The results revealed that Ro44-5912, at equivalent concentration, increased doxorubicin accumulation in P388ADR cells beyond that obtained with verapamil whereas no effects were seen with the parental P388 cells. The effect of Ro44-5912 on the binding of C219 monoclonal antibody to PGP in MDR cells was also studied and found not to decrease C219 expression on P388ADR cells.

Animals↗