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Biomedical subjects

W A Knight

Publications and source records attributed to W A Knight.

At least 19 recordsLinked to original sources
PubMed1990

Phase II trial of intravenous melphalan for metastatic colorectal carcinoma. A Southwest Oncology Group study.

Based on the high response rates seen among patients with colon cancer receiving high dose Melphalan with autologous marrow infusion, the Southwest Oncology Group conducted a Phase II trial of the compound at a conventional dose. The initial starting dose of 40 mg/m2 was reduced to 30 mg/m2 after severe myelotoxicity was encountered in the first five patients. Toxicity was primarily myeloid and was moderate to severe in most patients with one treatment related death. There were two complete and one partial response among 43 patients. Melphalan at 30 mg/m2 has little activity among patients with metastatic colorectal carcinoma.

Adult↗
PubMed1989

Pituitary abscess after autologous bone marrow transplantation.

The first case of pituitary abscess arising in a patient during recovery from autologous bone marrow transplantation is reported. A 31-year-old man with a 9 month history of T-cell lymphoma died suddenly more than 60 days after successful treatment with high-dose cyclophosphamide, total body irradiation, and autologous bone marrow infusion. Autopsy revealed a pituitary abscess associated with clinically silent sphenoid sinusitis. Unique aspects of this case are presented and clinical and pathologic features of pituitary abscess are reviewed. Although rare, pituitary abscess may complicate recovery from bone marrow transplantation.

Abscess↗
PubMed1987

CFU-GEMM correlate with neutrophil and platelet recovery in patients receiving autologous marrow transplantation after high-dose melphalan chemotherapy.

CFU-GEMM, multipotent progenitor cells, give rise to erythroid, granulocyte-macrophage and megakaryocytic cells. We have examined the utility of this assay for predicting hematologic recovery in patients treated with high-dose chemotherapy and autologous marrow rescue with cryopreserved marrow. In marrow samples from 50 patients CFU-E, BFU-E and CFU-GEMM significantly decreased following cryopreservation. The median value for CFU-E declined from 132,659 to 10,648, BFU-E decreased from 36,112 to 3345 and CFU-GEMM decreased from 3242 to 260 colonies per ml of marrow frozen. Once cryopreserved, the number of CFU-E, BFU-E and CFU-GEMM remained stable with prolonged storage in liquid nitrogen. In 48 patients uniformly treated with high-dose melphalan (180 mg/m2) and rescued with cryopreserved autologous marrow, univariate analyses showed that the time to platelet recovery (greater than 50 x 10(9)/l) was correlated with the number of CFU-E, BFU-E and CFU-GEMM infused (p less than 0.05). The time to neutrophil recovery was only correlated with the number of BFU-E and CFU-GEMM infused (p less than 0.01). However, by multivariate analyses, only the number of CFU-GEMM, and not CFU-E and BFU-E, infused correlated both with the time to neutrophil and platelet recovery. These data indicate that the CFU-GEMM assay may be useful for determining the repopulating ability of cryopreserved bone marrow.

Bone Marrow↗
PubMed1986

Phase II trial of high-dose melphalan and autologous bone marrow transplantation for metastatic colon carcinoma.

Colon carcinoma, the second leading cause of cancer-related deaths in the United States, is resistant to chemotherapy in a large majority of cases. Single-agent and combination chemotherapy have failed to prolong survival. New approaches are clearly needed. In experimental models, a steep dose-response curve for colorectal cancer has been demonstrated using various agents. The hematopoietic toxicity of high-dose therapy with these drugs can be circumvented by autologous bone marrow transplantation. We investigated the use of high-dose melphalan with autologous bone marrow rescue in 20 patients with metastatic colon carcinoma. Each patient received melphalan, 180 mg/m2 intravenously (IV), followed eight hours later by bone marrow infusion. Median duration of granulocytopenia (less than 500 neutrophils/microL) was twelve days (range, 5 to 35 days), while transfusion-dependent thrombocytopenia (less than 20,000 platelets/microL) had a median duration of eight days (range, 3 to 23 days). Time to bone marrow engraftment was not affected by prior 5-fluorouracil therapy. Nausea and vomiting occurred in 14 patients but was generally short lived. Mild stomatitis, esophagitis, and diarrhea were common. Severe gastrointestinal (GI) side effects did not occur. One treatment-related death occurred secondary to intramural tumor necrosis, which resulted in massive lower GI bleeding. Complete responses were observed in three patients (15%) and partial responses in six patients (30%), for an overall response rate of 45%. Median survival was 198 days in this group of patients with extensive disease. High-dose melphalan therapy for metastatic colon carcinoma, when used with autologous bone marrow transplantation, appears to achieve a high response rate with tolerable toxicity. Further investigation is needed to define the role of this therapy in the care of advanced colon carcinoma.

Adult↗
PubMed1986

Use of in vitro dose response effects to select antineoplastics for high-dose or regional administration regimens.

Several preclinical and clinical studies have documented that dose or dose intensity of chemotherapeutic agents are important factors for response of patients' tumors. This finding has prompted empiric trials of certain chemotherapeutic agents in high-dose or regional administration treatment regimens. The present study was performed to identify agents that would be particularly good candidates for high-dose or regional administration regimens against particular types of tumors. Using a human tumor cloning technique, we constructed dose in vitro response lines for ten different chemotherapeutic agents against seven different histologic types of malignancies. Slopes of the lines indicated the agents with the greatest increases of in vitro response per increment in dose of the agent. Tumors against which the agents gave the steepest dose response lines included lymphoma, head and neck cancer, ovarian cancer, and small-cell lung cancer, while the dose response lines for non-small-cell lung cancer, breast cancer, and colon cancer were quite flat. Suggestions for clinical trials based on these findings include the use of high-dose melphalan for patients with lymphoma, head and neck, and ovarian cancer; the use of mitoxantrone in high-dose regimens for patients with breast cancer; high-dose cisplatin regimens for patients with small-cell lung cancer; high-dose bleomycin regimens for patients with non-small-cell lung and head and neck cancer; and regional perfusion of liver metastases from colorectal cancer with cisplatin. Prospective testing of high-dose or regional administration regimens suggested by this new model should indicate its use for prediction of the best agent to use in high-dose regimens against a particular tumor type.

Antineoplastic Agents↗
PubMed1985

Adjuvant therapy for breast cancer with positive axillary nodes designed according to estrogen receptor status.

This is a preliminary report of the Southwest Oncology Group--Adjuvant Therapy in Operative Breast Cancer with Positive Axillary Nodes--in which therapy is randomized by estrogen receptor (ER) data. ER--patients receive either 1 or 2 years of CMFVP. The ER + group receive CMFVP for 1 year and/or hormonal therapy. ER + patients have a significant longer disease-free interval compared to ER--patients (P = 0.004). There was no significant difference in disease-free interval for ER--patients who receive either 1 or 2 years of CMFVP. The data for ER + patients is too preliminary to report for disease-free or total survival. Toxicity is acceptable because of frequent monitoring and examinations which results in the low percentage of life-threatening toxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Methyl-glyoxal bis guanyl hydrazone (methyl-GAG, MGBG) in advanced breast cancer. A Phase II trial of the Southwest Oncology Group.

The Southwest Oncology Group has evaluated methyl-GAG on a weekly schedule among patients with metastatic breast cancer. Among 72 fully and partial evaluable patients, one complete and four partial responses were seen. Toxicity was similar to other trials with this compound except for thrombocytopenia which was more frequent and severe and probably related to tumor infiltrating marrow. In addition, one patient experienced recall dermatitis following methyl-GAG. This toxicity has not been previously reported with this compound. Methyl-GAG has minimal activity at this dose and schedule among heavily pretreated patients with breast cancer.

Adult↗
PubMed1983

Mitoxantrone in advanced breast cancer: a phase II trial of the Southwest Oncology Group.

124 patients with metastatic breast cancer were entered into this phase II trial of mitoxantrone (DHAD). Patients were stratified prior to treatment as good or poor risk, and whether they had received previous therapy with an anthracycline derivative. Mitoxantrone was given every 21 days at a starting dose of 12 mg/m2 for good risk patients and 10 mg/m2 for poor risk patients. Among the group who had not received anthracyclines, 12 are fully or partially evaluable for response with five classified as good risk. One complete response, ongoing at 52 weeks was seen in this group. Of the seven poor risk patients, stable disease was seen in two. 103 patients with prior anthracycline exposure are fully or partially evaluable, 31 good risk and 72 poor risk. There were three partial responses in each group. Toxicity was primarily myelosuppression, and was more severe in the poor risk group. Mitoxantrone when used on this schedule has minimal activity among heavily pretreated patients with metastatic breast cancer.

Adult↗
PubMed1983

High dose chemotherapy with autologous marrow rescue in the treatment of resistant solid tumors.

Toxicity in the form of marrow suppression has hampered the investigation of intensive chemotherapy as it applies to the treatment of solid tumors. The use of autologous marrow rescue to ameliorate protracted aplasia permits the application of high dose chemotherapy to the treatment of solid tumors. We review the theoretical limitations of this technique and present results reported in selected solid tumors. Autologous marrow rescue from intensive chemotherapy is an innovative approach in overcoming the resistence to chemotherapy that is typical of solid tumors. The role of this therapy in the treatment of solid tumors remains to be defined.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

Pharmacokinetics of high dose melphalan.

A pharmacokinetic study of high dose intravenous melphalan, 180 mg/m2, was performed in eight patients. Plasma levels of melphalan declined in a biexponential fashion with a mean terminal half-life (t 1/2 beta) of 61 min (range 40.3-132.8 min). Estimated peak concentrations ranged from 5.45 to 16.57 mcg/ml. The average volume of distribution at steady state (Vdss) and clearance were 0.479 +/- 0.164 l/kg and 6.73 +/- 1.60 ml/min/kg, respectively. These kinetic parameters are similar to those reported from studies using lower doses of melphalan.

Adult↗
PubMed1983

Phase II evaluation of MGBG in non-small cell carcinoma of the lung. A Southwest Oncology Group study.

One hundred and eight patients with non-small cell lung cancer were treated in a Phase II trial with MGBG at a dose of 600 mg/m2 i.v. weekly. Partial responses were noted in 3/43 patients with adenocarcinoma and 1/40 with squamous cell carcinoma. No responses were noted in 24 patients with large cell carcinoma. Overall, the drug was reasonably well-tolerated. At this dosage and schedule, MGBG has no substantial antitumor activity for patients with non-small cell lung cancer.

Drug Evaluation↗
PubMed1983

Methyl-glyoxal bis guanyl hydrazone (methyl-GAG, MGBG) in lymphoma and Hodgkin's disease. A Phase II trial of the Southwest Oncology Group.

The Southwest Oncology Group has evaluated methyl-GAG on a weekly schedule among patients with lymphoma and Hodgkin's disease. Among 56 fully and partially evaluable patients responses were seen in 3 of 10 patients with Hodgkin's disease and 11 of 46 patients with lymphoma. Toxicity was acceptable. Methyl-GAG has significant antitumor activity among this group of heavily pretreated patients. Additional trials of methyl-GAG in combination with other agents are underway.

Adolescent↗
PubMed1983

Adjuvant therapy of breast cancer: the Southwest Oncology Group experience.

The Southwest Oncology Group in a prospective randomized study compared one year of adjuvant combination chemotherapy with continuous CMFVP (cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone) to two years of intermittent L-phenylalanine mustard (L-PAM) in women with operable breast cancer with histologically positive axillary lymph nodes. In fully and partially evaluable patients with a 68-month median follow-up, treatment failures have occurred in 27% of 172 receiving CMFVP and 47% of 186 women given L-PAM (p = 0.002). The advantage for women receiving CMFVP was seen for all subsets regardless of menopausal status except among women who were premenopausal and had 1-3 positive nodes. Based on this study, a second study was implemented using both the estrogen-receptor (ER) content of the primary tumor and axillary nodal status to select therapy.

Antineoplastic Combined Chemotherapy Protocols↗