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Biomedical subjects

C L Vogel

Publications and source records attributed to C L Vogel.

At least 19 recordsLinked to original sources

Survival after first recurrence of breast cancer. The Miami experience.

BACKGROUND: Four hundred thirty-three patients with recurrent breast cancer were treated by the authors at a large medical breast oncology facility from 1976-1982. The median survival time from first relapse (MSFR) for the 193 patients whose survival experience was not confounded by lead-time bias was 26 months. This MSFR is similar to that of most series published in the 1970s and 1980s and is approximately double that of series published in the 1960s. METHODS: In this series, regression analysis identified disease-free interval (DFI), estrogen receptor (ER) status, and dominant disease site as significant prognostic variables, similar to other published series. RESULTS: In 113 patients with known ER values, DFI, and dominant metastatic sites, a prognostic spectrum of MSFR patterns was identified among combinations of these three variables. The MSFR ranged from 15 months for poor risk patients with negative ER values, visceral dominant sites, and DFI of less than 24 months, to more than 90 months for good risk patients with positive ER values, soft tissue dominant sites, and DFI of more than 24 months. Although menopausal status alone was not a significant prognostic variable in regression analysis, 66% of premenopausal patients had a constellation of "poor" prognostic variables. CONCLUSIONS: This type of prognostic factor analysis at first relapse could help identify subsets of patients who might be considered for aggressive investigational therapies such as high-dose chemotherapy with autologous bone marrow reconstitution.

Breast Neoplasms

Postsurgical adjuvant chemotherapy with or without radiotherapy in women with breast cancer and positive axillary nodes: a South-Eastern Cancer Study Group (SEG) Trial.

In a prospective study of 622 women with breast cancer, those with one to three histologically positive axillary lymph nodes were randomised after mastectomy to receive cyclophosphamide 100 mg/m2 orally on days 1-14, methotrexate 40 mg/m2 intravenously on days 1 and 8, and fluorouracil 600 mg/m2 intravenously on days 1 and 8 every 28 days for six cycles (CMF x six), or for twelve cycles of the same chemotherapy (CMF x 12). Those with > or = four positive nodes were randomised to one of these two groups or to 5000 cGy of postmastectomy regional radiotherapy (RT) followed by six cycles of the same chemotherapy (RT + CMF x six). With about 10 years median follow-up, there was no significant difference in survival or disease-free survival among the three groups. There was evidence of decreased locoregional recurrence in patients with > or = four nodes who received RT + CMF x six (relative risk 0.53, P = 0.067). Multivariate analysis indicated that the presence of > or = four positive nodes (negatively) and the percentage of ideal (full) dose of CMF received (positively) were the strongest factors predictive of survival. This study shows no advantage for 12 over six cycles of CMF chemotherapy in women with breast cancer and positive axillary nodes. There was a suggestion of decreased locoregional recurrence but no improvement in survival with radiotherapy for women with > or = four positive nodes.

Adult

Treatment of metastatic breast cancer.

Relapse of breast cancer connotes a dire prognosis. However, long-term survival with remissions and disease exacerbation are possible using conservative treatment strategies and often sequential hormonal manipulations. Hormonal therapy is the mainstay of metastatic breast cancer treatment for patients with hormonally sensitive tumors; cytotoxic chemotherapy, for patients with hormonally independent tumors. High-dose chemotherapy with autologous bone marrow reinfusion is currently under investigation.

Breast Neoplasms

Dronabinol and prochlorperazine in combination for treatment of cancer chemotherapy-induced nausea and vomiting.

Dronabinol (Marinol, Roxane Laboratories, Columbus, OH) and prochlorperazine were tested alone and in combination in a randomized, double-blind, parallel group, multicenter study. Patients were randomized to receive either 1) dronabinol 10 mg every 6 hr plus placebo; 2) placebo plus prochlorperazine 10 mg every 6 hr; or 3) dronabinol and prochlorperazine, each 10 mg every 6 hr. Antiemetic treatment was begun 24 hr prior to and continued for 24 hr after the last dose of chemotherapy; all was given orally. Only 29% of patients in group 3 versus 47% in group 1 and 60% in group 2 experienced nausea after chemotherapy. In addition, the median duration per episode and severity of nausea were significantly less with combination therapy. Vomiting occurred after chemotherapy in 41%, 55%, and 35% of patients in groups 1, 2, and 3, respectively. The median duration per episode of vomiting was 1 min in group 3 versus two in group 1 and four in group 2. Side effects, primarily CNS, were more common in group 1 than in group 2; addition of prochlorperazine to dronabinol appeared to decrease the frequency of dysphoric effects seen with the latter agent. The combination was significantly more effective than was either single agent in controlling chemotherapy-induced nausea and vomiting.

Adult

A phase I study of 4'-0-tetrahydropyranyladriamycin. Clinical pharmacology and pharmacokinetics.

A Phase I study of intravenous (IV) bolus 4'-0-tetrahydropyranyladriamycin (Pirarubicin) was done in 55 patients in good performance status with refractory tumors. Twenty-six had minimal prior therapy (good risk), 23 had extensive prior therapy (poor risk), and six had renal and/or hepatic dysfunction. A total of 167 courses at doses of 15 to 70 mg/m2 were evaluable. Maximum tolerated dose in good-risk patients was 70 mg/m2, and in poor-risk patients, 60 mg/m2. The dose-limiting toxic effect was transient noncumulative granulocytopenia. Granulocyte nadir was on day 14 (range, 4-22). Less frequent toxic effects included thrombocytopenia, anemia, nausea, mild alopecia, phlebitis, and mucositis. Myelosuppression was more in patients with hepatic dysfunction. Pharmacokinetic analyses in 21 patients revealed Pirarubicin plasma T 1/2 alpha (+/- SE) of 2.5 +/- 0.85 minutes, T beta 1/2 of 25.6 +/- 6.5 minutes, and T 1/2 gamma of 23.6 +/- 7.6 hours. The area under the curve was 537 +/- 149 ng/ml x hours, volume of distribution (Vd) 3504 +/- 644 l/m2, and total clearance (ClT) was 204 + 39.3 l/hour/m2. Adriamycinol, doxorubicin, adriamycinone, and tetrahydropyranyladriamycinol were the metabolites detected in plasma and the amount of doxorubicin was less than or equal to 10% of the total metabolites. Urinary excretion of Pirarubicin in the first 24 hours was less than or equal to 10%. Activity was noted in mesothelioma, leiomyosarcoma, and basal cell carcinoma. The recommended starting dose for Phase II trials is 60 mg/m2 IV bolus every 3 weeks.

Adult

Evaluation of human chorionic gonadotropin and alpha fetoprotein in benign and malignant testicular disorders.

The marker proteins alpha fetoprotein and human chorionic gonadotropin are useful adjuncts to clinical evaluation of patients with non-seminomatous testicular germ cell malignant growths during and after therapeutic interventions. Measuring both markers is better than measuring either one alone. An elevated marker assay indicates the presence of active disease. A normal marker assay does not exclude active disease being present. Lastly, these markers are of limited usefulness in the evaluation of undiagnosed testicular masses.

Adolescent

A phase II study of adriamycin (NSC 123127) in patients with hepatocellular carcinoma from Zambia and the United States.

Nineteen Zambian and 22 American patients with hepatocellular carcinoma were treated with Adriamycin every three weeks in intravenous doses ranging from 20-75 mg/m2 (depending upon their initial serum bilirubin levels). Four of 16 (25%) "good risk" Zambian and American patients who received 75 mg/m2 had objective responses, while in five additional patients there was evidence of either transient tumor regression or disease stabilization. In contrast three of 25 "poor risk" patients who received 20-60 mg/m2 had objective responses. Even in this latter group, however, transient, objective signs of tumor regression were noted in four patients. The results of the present study confirm previous reports suggesting anti-tumor activity for high doses of Adriamycin in hepatocellular carcinoma. Since those responses seen were generally incomplete and transient, further clinical trials of this agent used in combination or sequentially with other agents are indicated.

Adult

Hepatitis B virus infection and primary hepatocellular carcinoma.

Ninety-three patients with biopsy-proven primary hepatocellular carcinoma (PHC) from Uganda, Zambia, and the United States were examined for serologic evidence of hepatitis B virus (HBV) infection. Patients were tested for hepatitis B surface antigen (HBsAg) and its antibody (anti-HBs), antibody to the hepatitis B core antigen (anti-HBc), hepatitis B e antigen (HBeAg), and its antibody (anti-HBe). Active HBV infection, as indicated by positive tests for HBsAg (with or without anti-HBs) and anti-HBc (without anti-HBs), was present in 62% of PHC patients (58 of 93), in contrast with 10% of African controls (9 of 90), and less than 1% of most United States adult populations reported in the literature. The presence of HBeAg or anti-HBe was rare among PHC patients and controls.

Adolescent

Effect of surgical and chemotherapeutic treatment on alpha-fetoprotein levels in patients with hepatocellular carcinoma.

Quantitative determinations of serum alpha-fetoprotein (AFP) by radioimmunoassay in 193 patients with hepatocellular carcinoma have demonstrated a wide variation in serum levels that appear to be relatively constant for each patient by the time that diagnosis is made. If there is no therapeutic intervention the serum AFP usually follows a gradual increase as the tumor progresses. A few patients have a fall in serum AFP as a preterminal event. Various forms of chemotherapy cause only minor and transient decrease in serum AFP. Surgical resection of tumor produces an immediate fall that parallels the catabolic decay rate for AFP. All AFP-positive patients treated with surgery had recurrence of their tumor with a rise in serum AFP preceeding clinical discovery. The correlation of serum AFP and effective treatment is demonstration of the usefulness of this oncofetal protein marker as an indicator of neoplastic activity for hepatocellular carcinoma and tumors with embryonal cell components and possibly for some other entodermally derived neoplasms.

Carmustine

Phase I trial of dianhydrogalactitol administered Iv in a weekly schedule.

Dianhydrogalactitol was given to 28 patients with a variety of advanced solid tumors on a weekly schedule in iv doses ranging from 2 to 80 mg/m2. No significant toxicity was encountered at doses up to 40 mg/m2/week for 4 weeks. At higher doses mild-to-moderate nausea and vomiting and hematologic toxicity were noted. Thrombocytopenia was more common than granulocytopenia and frequently resolved more slowly. No adverse drug-realted effects on liver, renal, coagulation, or cardiac function were seen. Although no patient had significant antitumor response (as strictly defined), objective improvement was noted in two patients, one with hypernephroma and the other with malignant melanoma. for phase II studies, a weekly dose of 70 mg/m2 is recommended for patients with normal hematopoiesis, with reduction by 25% (55 mg/m2) in patients with extensive prior radiation therapy, prior chemotherapy, and/or widespread metastasis to the bone.

Adult