Joan M. Bull

A randomized comparative trial of adriamycin versus methotrexate in combination drug therapy

A prospective randomized trial was conducted comparing the clinical response of 78 previously untreated patients with advanced metastatic breast cancer to a combination of cyclophosphamide, methotrexate, and 5‐fluorouracil (CMF) or to a combination of cyclophosphamide, adriamycin, and 5‐fluorouracil (CAF). Sixty‐two percent of the patients receiving CMF responded to treatment compared to an 82% response rate for the patients receiving CAF. Although within acceptable limits, hematologic and GI toxicity was greater with CAF. There was no significant difference in the duration of response to the two regimens. Therefore, the therapeutic difference between the two therapies is a higher initial response rate to the adriamycin containing regimen.

Kinetics of cis‐dichlorodiammineplatinum

The cancer chemotherapeutic cis‐dichlorodiammineplatinum (cis‐DDP) was administered to 8 patients (1‐hr intravenous infusion) at a dose of 70 mg/m2. Plasma and urine concentrations of platinum were determined by flame less atomic absorption spectrometry. Measured plasma platinum concentrations revealed a biphasic clearance of platinum with half‐life values of 23 min and 67 hr. Platinum values obtained 3 wk after the infusion indicated that a third excretory phase might be present. Urinary measurements showed 17 ± 2.7% of the administered dose excreted in the first 4 hr and 23 ± 3.9% excreted in the first 24 hr. Renal excretion appears to be predominantly by glomerular filtration. Non‐protein‐bound plasma platinum values were calculated and the non‐protein‐bound platinum was found to be rapidly and biphasically cleared from the plasma with half‐life values of 8 to 10 min and 40 to 45 min.

Whole Body Hyperthermia: A Phase-l Trial of a Potential Adjuvant to Chemotherapy

Fourteen patients with a variety of neoplasms not responsive to standard forms of therapy underwent whole body hyperthermia for a maximum 4 h at 41.8 degrees C. This was a phase-I cancer trial designed to develop whole body hyperthermia as an adjuvant to systemic chemotherapy. Intravenous analgesia was used to sedate patients, obviating the need for general endotracheal anesthesia. Hyperthermia was induced by means of a high-flow water perfusion suit. Cardiovascular performance was evaluated using a flow-directed pulmonary artery catheter. Patients developed a twofold mean increase in cardiac index without evidence of cardiac damage by ECG or creatine phosphokinase (CPK) isoenzymes. An acute fall in serum magnesium and phosphate and an acute rise in arterial pH, serum CPK values, and granulocyte count occurred in all patients. There were no clotting abnormalities. Toxicity included fatigue, diarrhea, nausea, and transient elevations in liver enzymes. Four patients were febrile for 36 h after initial defervescence. Peripheral neuropathy developed in four. These results show that with carefully monitored conditions whole body hyperthermia is feasible.

Electroencephalographic changes during whole body hyperthermia in humans

Abstract As part of a protocol of the National Cancer Institute, 21 selected patients were submitted to total body hyperthermia for treatment of metastatic carcinoma. Elevation body temperature up to 41.8°C for 2 h was achieved using a computer driven external heating system. Patients were sedated during treatment. To ensure the safety of the procedure, a battery of physiological parameters was monitored. Continuous EEG recordings were carried out in all patients. Analysis of the EEG included visual assessment, compressed spectral array and power spectrum. EEG data were compared mainly to body temperature, state of consciousness and drug administration. Consciousness during the treatment varied from very light sedation to light anesthesia, with some rare delirious episodes. No motor seizures were observed. All EEG recordings demonstrated major changes in both rhythmicity and amplitude (slower and lower) indicating a diffuse decrease of cortical activity during the hyperthermia period. All changes reversed themselves during the cooling period. Spectral power showed a statistically significant inverse relationship with temperature. At temperatures above 41°C, decrease in total EEG spectrum was not related to decrease in clinical reactivity. The degree of EEG slowing varied with the extent and duration of the hyperthermia, and was totally reversible within a few hours of cooling, without evidence of any EEG or neurological sequelae. However, at temperatures above 41.5°C, EEG changes compatible with metabolic or toxic encephalopathy were observed. Possible mechanisms are discussed.

Perspectives in the Treatment of Breast Cancer: 1976

Breast cancer is the major cancer killer of women in the United States. Recent advances in therapy promise more effective control of this illness. The development of hormone receptor analysis permits us to better understand the mechanisms of action of steroid and peptide hormones and increases the likelihood of using there hormonal agents effectively. Prospective surgical and surgical adjuvant trials offer the opportunity to define accurately the appropriate surgical procedure and most effective postoperative therapy after initial surgery. The development of chemotherapy, first singly and now in combination, has led to improved treatment of patients with advanced disease and defined better chemotherapy for use in adjuvant settings. The investigation of a matrix of marker substances in breast cancer may uncover new methods to assess residual disease and to monitor disease recurrence.

CYTOGENETICALLY ABNORMAL CELL S IN VITRO IN ACUTE LEUKÆMIA

Abstract Twenty patients with previously identified direct cytogenetic abnormalities were examined for persistence of the abnormality in both direct bone-marrow preparations and in-vitro methylcellulose cultures. Of seven patients with persistent direct abnormalities, four had these same cytogenetic abnormalities identified in cells from culture. In three patients with acute myelocytic leukaemia or a variant, these abnormalities had been previously associated with leukaemic cell lines. Cytogenetic markers in the cultured cells indicate that leukaemic cells from some patients can be grown in vitro.

Bone marrow involvement in breast cancer. Effect on response and tolerance to combination chemotherapy

Forty‐three patients with metastatic breast cancer who had not received prior chemotherapy were divided into two groups on the basis of whether or not a bone marrow examination revealed tumor. Both groups were treated with combination chemotherapy regimens and were analyzed with regard to response and toxicity parameters. The positive marrow group had a response rate similar to that of the negative marrow group (67% vs 71%), and a slightly shorter median time to progressive disease (240 vs 258 days) and median duration of remission (213 vs 243 days). The positive marrow group had higher requirements for hematologic support and tended to have more infectious complications. The data suggest that metastatic breast cancer patients with a bone marrow examination revealing tumor, although requiring more supportive care, may be treated as effectively with combination chemotherapy as those patients in whom the marrow examination does not reveal tumor.