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Biomedical subjects

A Barlock

Publications and source records attributed to A Barlock.

12 recordsLinked to original sources

Treatment of poor prognosis nonseminomatous testicular cancer with a "high-dose" platinum combination chemotherapy regimen.

A new intensive four drug combination chemotherapy regimen, termed PVeBV, consisting of cis-platinum, vinblastine, bleomycin, and VP-16, was administered to six previously untreated patients with poor prognosis advanced nonseminomatous testicular cancer and to four patients who had relapsed on primary platinum based regimens. The cis-platinum was administered in 250 ml of 3% saline at twice the dose (40 mg/m2 IV days 1-5 every three weeks) used in other treatment schedules. All six previously untreated patients achieved a complete remission. Four achieved a complete remission with three cycles of PVeBV while the other two patients achieved a complete remission with an additional cycle of cisplatinum and VP-16 at 200 mg/m2 IV X five followed by autologous bone marrow infusion. All four relapsed patients responded to PVeBV (two complete remissions and two partial remissions). There were no deaths associated with PVeBV therapy; however, myelosuppression was severe. There has been no renal toxicity (other than hypomagnesemia) observed with 35 cycles of high-dose platinum therapy in previously untreated patients. These results indicate that PVeBV is a promising chemotherapy regimen for the treatment of poor prognosis testicular cancer patients. Furthermore, it appears that cis-platinum can be administered at higher doses than previously used without an increase in renal toxicity if administered in hypertonic saline. The high-dose cis-platinum schedule, as used in PVeBV, warrants evaluation in other tumors which respond to standard-dose platinum therapy.

Antineoplastic Agents↗

Persistent hypomagnesemia following cisplatin chemotherapy for testicular cancer.

Twenty-nine patients with nonseminomatous germ cell tumors of the testis have been followed for a median of 1.9 years (range 0.3-3.6) following completion of cisplatin-containing combination chemotherapy. Twenty-two of the 29 patients (76%) became hypomagnesemic during chemotherapy and, of these, 11 (50%) have remained persistently hypomagnesemic for as long as 3 years following discontinuation of cisplatin treatment. In the remaining patients, serum Mg levels returned to normal a median of 0.6 years (range, 0.2-2.1) after completion of chemotherapy. In eight of nine persistently hypomagnesemic patients studied, urinary Mg excretion was inappropriately elevated. Symptoms attributable to hypomagnesemia were rarely reported, although muscle cramps, twitching, or mild tremor were noted by the most severely hypomagnesemic patients. Continued followup of these patients is required to determine the effects of chronic hypomagnesemia in man.

Cisplatin↗

Defective monocyte killing in patients with malignancies and restoration of function during chemotherapy.

Spontaneous monocyte-mediated cytotoxicity (SMMC) in 34 patients treated with a chemotherapeutic regimen including cisplatin for various malignancies was depressed (median 7% 51Cr release) compared with SMMC in 31 normal controls (median 43%; p < 0.0001). Cytotoxicity in 7 patients with stage III or IV ovarian carcinoma was then followed during six cycles of chemotherapy with a cisplatin-containing regimen. All patients had initial cytotoxic values of < 8%, and in all SMMC increased at least three-fold between the third and fifth cycle of chemotherapy. This study lends support to the concept that cancer patients have depressed monocyte function. Cisplatin-containing chemotherapy seems to enhance monocyte function in vitro and in vivo.

Cisplatin↗

Changes in multiple or sequential estrogen receptor determinations in breast cancer.

Estrogen receptor (ER) analyses are widely used in the management of patients with breast cancer. Few data are available concerning variations in ER as a function of time and therapy. We examined patients in whom multiple biopsies and receptor analyses were either performed simultaneously or over time with or without intervening chemotherapy or endocrine therapy. In 27 patients with simultaneous assays from different metastatic sites, concordant results were obtained in 23 (85%) with respect to classifying a tumor as ER+ or ER-. In 34 patients, multiple assays were performed over time. The receptor concentrations were concordant in patients receiving no intervening therapy. In 10 patients receiving hormonal therapy, the median receptor concentration changed from 66 femtomoles per mg cytoplasmic protein pretherapy to 8 femtomoles post therapy (P less than 0.05). This change suggested that hormonal therapy selectively eliminates ER+ cells. In 19 patients receiving intervening chemotherapy, the median receptor concentrations pre and post therapy were similar. We conclude that simultaneous assays from multiple metastatic sites are highly concordant and unlikely to change over time without intervening therapy, but marked changes occur following therapy with a decrease in receptor concentration after endocrine therapy.

Antineoplastic Agents↗

Estrogen receptor values in patients with benign breast disease.

Tissue specimens from 55 female patients with benign breast disease were assayed for estrogen receptor. Twenty-one of 55 patients (38%) had tumors which contained significant amounts of estrogen receptor (greater than 10 femtomoles/mg protein). Fibroadenomas possessed estrogen receptor more frequently than fibrocystic disease or other benign breast tumors. Estrogen receptor positivity did not correlate with laterality of the tumor; location or size of the largest nodule. Patients with estrogen receptor positive tumors had a mean age of 26.9 years compared to 36.4 years for patients with estrogen receptor negative tumors (p less than 0.01). Twenty of 46 (43%) premenopausal patients had benign tumors which were estrogen receptor positive compared to zero of 8 postmenopausal patients (p less than 0.05).

Adenofibroma↗

Distribution, frequency, and quantitative analysis of estrogen, progesterone, androgen, and glucocorticoid receptors in human breast cancer.

The distribution and frequency of steroid hormone receptors are described 329 patients with breast cancer. The distribution of each of the steroid hormone receptors is unimodal with a progressive increase in the proportion of patients positive at lower receptor values. Receptor values expressed as fmol/mg cytoplasmic protein are well correlated with values expressed as fmol/mg breast tumor. Estrogen receptor was positive in 53% of the patients; progesterone receptor was positive in 38% of the patients; glucocorticoid receptor was positive in 52% of the patients; and androgen receptor was positive in 31% of the patients. The type of tissue assayed did not affect steroid hormone receptor positivity. For primary tumors, there was no correlation between steroid hormone receptor positivity and location of the tumor in the breast, size of the tumor, or extent of the disease. Each of the steroid hormone receptors was positively associated with each of the other steroid hormone receptors. Estrogen receptor was correlated with menopausal status and axillary nodal status, but these correlations did not exist for the other steroid hormone receptors. Estrogen receptor was not correlated with age after adjustment for menopausal status. The other steroid hormone receptors were not correlated with age.

Adult↗

Association between steroid hormone receptor status and disease-free interval in breast cancer.

The possibility of an association between steroid hormone receptor status and disease-free interval was examined in 292 patients with breast cancer. Estrogen receptor positivity was associated with a prolonged disease-free interval. This association was independent of age, menopausal status, tumor size, or nodal status. There was no association between the presence or absence of progesterone, androgen, or glucocorticoid receptor and disease-free interval.

Adult↗

The relation between estrogen receptors and response rate to cytotoxic chemotherapy in metastatic breast cancer.

In a retrospective study we determined the relation between estrogen receptors and the response rate to cytotoxic chemotherapy in 70 patients with metastatic breast cancer. Thirty-four of 45 patients with low or absent estrogen-receptor values (less than 10 fmol per milligram of cytoplasmic protein) had objective responses to chemotherapy, whereas only three of 25 patients with higher values (greater than 10 fmol per milligram of cytoplasmic protein) responded (P less than 0.0001). There were no statistically significant differences between the two groups in age, menopausal status, disease-free interval, Karnofsky index or prior therapy. Differences in sites of involvement or type of chemotherapy did not account for the increased response rate in receptor-negative patients. We conclude that estrogen-receptor values are an important predictor of response to cytotoxic chemotherapy in metastatic breast cancer.

Adult↗

Association between steroid hormone receptors and response rate to cytotoxic chemotherapy in metastatic breast cancer.

The influence of steroid hormone receptors on response rate to cytotoxic chemotherapy in 70 patients with metastatic breast cancer was determined in a retrospective study. We have previously reported that 34 of 45 patients with tumors containing low or absent estrogen-receptor values had objective responses to chemotherapy while three of 25 patients with positive estrogen-receptor tumors responded. In the present study, 22 of 34 patients with low or absent progesterone-receptor tumors had an objective response to cytotoxic chemotherapy, while none of eight patients with a positive progesterone-receptor tumor responded (P less than 0.05). Patients having tumors with a negative estrogen receptor and a negative progesterone receptor had a response rate of 88% (21 of 24 patients). There were three patients whose tumors were estrogen-receptor negative but progesterone-receptor positive; none had a response to chemotherapy. Chemotherapy response was not associated with the presence or absence of either androgen or glucocorticoid receptor. We conclude that progesterone-receptor values in addition to estrogen-receptor status may prove to be important correlates of response to cytotoxic chemotherapy in metastatic breast cancer. Androgen- and glucocorticoid-receptor analyses are not helpful in predicting response to chemotherapy.

Adult↗

Chemotherapy for testicular cancer: current status of the National Cancer Institute Combined Modality Trial.

Twenty-five previously untreated patients with advanced testicular carcinoma were treated with a five-drug combination chemotherapy program containing cis-dichlorodiammineplatinum(II). This drug regimen was used as part of a trial testing the efficacy of cytoreductive surgery (15 patients) and in ten additional patients not eligible for the combined modality study. Eleven of 25 (44%) patients had a complete response and 11 of 25 (44%) patients had a partial response. Nine of 11 (82%) patients with minimal tumor burden upon initiation of chemotherapy had a complete response. With a median followup of 12+ months, none have relapsed. Complete remissions in patients with very advanced bulky disease were rare (two of 14 [14%] patients) and of short duration, with both patients relapsing. In addition to the usual hematologic toxicity, 14 of 25 (56%) patients developed hypomagnesemia and five of 25 (20%) patients developed systemic reactions to cis-dichlorodiammineplatinum(II) which prevented further drug administration.

Adolescent↗