Reginald P. Pugh

5-fluorouracil given once weekly: Comparison of intravenous and oral administration

One hundred seven patients with disseminated adenocarcinoma were randomized to receive 5‐Fluorouracil (5‐FU) by vein, Group A (52 patients), or by mouth, Group B (55 patients). Dosage for both groups was 15 mg/kg body weight given once weekly. Clinically useful response rate was 21% for Group A (IV) and 40% for Group B (oral). Duration of response and mean cumulative dose to beginning response were comparable in both groups. Slight differences were observed in toxicities in the 2 groups. G.I. toxicity was more frequent in Group B (oral) and hematologic toxicity was more common in Group A (IV).

Treatment of cancer with weekly intravenous 5-fluorouracil. Study by the Western Cooperative Cancer Chemotherapy Group (WCCCG)†

5‐Fluorouracil (5‐FU) has usually been administered by rapid intravenous injection of 15 mg/kg daily for 3‐5 days and 7.5 mg/kg every 2 or 3 days to toxicity, repeated monthly (antitumor response about 10‐30%). Drug morbidity and mortality have been excessive. Modifications of this course have shown similar response rates but decreased toxicity and mortality. In the present WCCCG study, 548 patients with disseminated cancer were treated weekly with 5‐FU, without a loading dose, by rapid intravenous injection, beginning at 15 mg/kg/week for one month, and increased to 20 mg/kg/week (if necessary) to levels producing mild toxicity or an antitumor effect. Of the 339 patients now evaluated for response, 6 had complete responses, 54 had decreases in tumor size > 50%, and 34 had decreases in tumor size of 25‐50%. The response rates > 50% (I‐B and I‐C) for adenocarcinoma of the breast, stomach, and colon were 37.8%, 28.6%, and 16%, respectively. Of the 430 patients evaluated for toxicity, 62 manifested no toxicity, and 368 patients had mild‐to‐severe toxicity. There were 8 drug‐related deaths in patients who received 5‐FU in dosages higher than those allowed in the protocol. There were no drug deaths in patients who received 5‐FU as stipulated by the protocol.

Single‐dose quinacrine (atabrine) and thoracostomy in the control of pleural effusions in patients with neoplastic diseases

Thirty‐nine patients with various malignant tumors developed intractable malignant effusions. The response rate in 12 patients given intracavitary quinacrine in small daily doses was 67%. Quinacrine was administered as a single dose through a thoracostomy tube in 27 patients. The response rate was 70%. There was no significant difference in useful response observed whether lung metastases were demonstrated or not. Signs and symptoms of quinacrine toxicity were observed in both patient groups with more of the disturbing and serious toxicity noted in the group receiving a single dose.

clinical experience with procarbazine in Hodgkin's disease, reticulum cell sarcoma, and lymphosarcoma

Seventy‐two patients with Hodgkins diseasereticulum cell sarcomalymphosarcomaand various other malignant neoplasms were treated with the methylhydrazine derivative procarbazine hydrochloride (Matulane, NSC‐77213). Response to therapy could be evaluated in 50 patients. Favorable responses occurred in 22 of 33 evaluable patients with Hodgkins disease2 of 5 patients with reticulum cell sarcomaand 2 of 5 patients with lymphosarcoma. All of the responders had previously shown resistance to at least 2 other antitumor agents. Toxic effects of therapy included leukopeniathrombocytopenianauseavomitingstomatitislethargyataxiaand alopecia. Median time to start of response was 21 days; median cumulative dose to start of response was 51.3 mg/kg. Responses lasted a median of 98 days (range: 34‐322 days). Procarbazine is a useful agent in advanced lymphomas.

Metastatic carcinomatosis of the liver mimicking cirrhosis: Case report and review of the literature

Carcinomatous involvement of the liver mimicking cirrhosis is a rare complication of metastatic carcinoma, most frequently seen with scirrhous carcinoma of the breast. The case of a 46‐year‐old woman with breast carcinoma presenting with ascites, jaundice, spider angiomata, and portal hypertension is reported. On hepatic scan the liver appeared to be almost the same size as the spleen, a finding frequently seen in cirrhosis. A chemotherapeutic program was introduced, but was of no benefit, and the patient died with uncontrolled esophageal bleeding. The prominent histologic feature on autopsy was intense stromal fibrosis and intravascular tumor infiltration with compression of vessels of the portal system.

Radiation-induced leiomyosarcoma of the great vessels presenting as superior vena cava syndrome

A patient with a pleomorphic intravascular leiomyosarcoma of the great vessels of the neck and mediastinum presented clinically with a superior vena cava syndrome. A latent period of 29 years elapsed between receiving orthovoltage radiation to the neck and right side of chest to treat recurrent ganglioneuroblastoma, and the appearance of a leiomyosarcoma and subsequent recurrences. The patient underwent partial resection of the tumor, received adjunct chemotherapy, and was shown to be free of disease by clinical tests and by magnetic resonance imaging (MRI) 17 months after completion of chemotherapy. The criteria for the diagnosis of radiation‐induced sarcomas are reviewed in relation to the present case. The critical role of magnetic resonance imaging in both the diagnosis and continued follow‐up of the patient is described. This would appear to be the first reported case of radiation‐induced intravascular leiomyosarcoma of the great vessels of the neck and mediastinum presenting as a superior vena cava syndrome.

Short-term chemotherapy of poor-prognosis metastatic breast cancer with three non-cross resistant chemotherapy regimens. A Southwest Oncology Group Study.

A Southwest Oncology Group pilot study was designed to evaluate a brief, 4.5‐month induction course of chemotherapy with three presumably non‐cross resistant regimens in poor‐prognosis metastatic breast cancer. Sixty‐three patients were treated with doxorubicin, cyclophosphamide, plus vincristine on day 1, methotrexate followed 30 minutes later by 5‐fluorouracil (5‐FU) on day 22, and mitomycin C plus 3 days of vinblastine on day 43. All three sequential regimens were repeated once and therapy was then discontinued in responding patients. The same chemotherapy was reinstituted at the time of relapse. The overall response rate to the induction chemotherapy was 35% and included only one complete response (2%). Median response duration was 9 months. Respondents were off all therapy for a median of 5 months (range, 1–12+ months) and were followed without evidence of progressive disease. Response to retreatment was 30% with no complete responses seen. Overall median survival from the data of diagnosis of metastatic disease was 24 months, with a median survival of 14 months from the date of initiation of therapy. Toxicity for this induction regimen was moderate with two treatment‐related deaths secondary to myelosuppression. While the results of this pilot study fail to support the use of non‐cross resistant regimens in breast cancer, short‐term therapy appears to have no adverse effect on survival and resulted in significant periods during which no therapy was given, resulting in a reduction in overall toxicity. Cancer 59:239–244, 1987.

Treatment of advanced breast carcinoma with 5‐fluorouracil: A randomized comparison of two routes of delivery

Fifty‐one patients with metastatic breast carcinoma were randomized to treatment with weekly 5‐fluorouracil (5‐FU) either by mouth or intravenously. Prior treatment included radiation therapy (75%), chemotherapy (27%), and hormonal therapy (86%). Response frequency (tumor reduction ≤50%) in the 49 evaluable patients was 24% (6/25) for oral vs. 29% (7/24) for intravenous administration. Disease was stable in an additional 13% of patients treated intravenously and 20% of patients treated orally. Median survival was 9.8 months for intravenously treated patients and 12.1 months for orally treated patients (N.S.). A multivariate model of survival, to adjust for imbalance between treatment groups, also showed comparable survival in the two groups. Neither response nor survival was significantly correlated with nadir granulocyte count. Weekly oral 5‐FU results in comparable response and survival to 5‐FU given intravenously, consistent with a relatively low dose–response relationship for 5‐FU in breast carcinoma.

Phase II trial of trimetrexate in untreated advanced gastric carcinoma. A Southwest Oncology Group study.

SummaryTwenty-three evaluable patients with advanced gastric adenocarcinoma were treated with trimetrexate at doses of 8–12 mg/m2 intravenously daily for five days, with cycles repeated every 21 days. One complete response was seen for an overall response rate of 4% (95% confidence interval 0–22%). Hematologie toxicities of grade ≥ 3 were seen in 10/23 patients, and overall any grade 3 or greater toxicity was seen in 14/ 23 patients. Trimetrexate has minimal activity against gastric adenocarcinoma in this study, and no further investigation of this agent at this dose and schedule is recommended in this disease.

Doxorubicin and Methotrexate on a Weekly Schedule in Patients with Sarcomas

Fifty-five sarcoma patients with advanced measurable disease were treated with a doxorubicin and methotrexate combination in which both drugs were given on a weekly schedule. Patients received doxorubicin and methotrexate at three prospectively evaluated treatment levels with doxorubicin dosage ranging from 0.5 to 0.725 mg/kg/week and methotrexate dosage ranging from 0.25 to 0.375 mg/kg/week. Objective responses were seen in 11 of 39 (28%) patients receiving the two higher doxorubicin-methotrexate treatment levels where doxorubicin dose was greater than 0.5 mg/kg/week compared to only 2 of 16 (12%) patients receiving lower doxorubicin levels (p less than 0.05), suggestive of a dose-response relationship. Toxicity of this regimen was manageable but stomatitis was appreciable, seen in 30% of patients. These results support the activity of weekly doxorubicin in sarcoma therapy. However, no apparent improvement was associated with addition of conventional dose methotrexate to weekly doxorubicin treatment.