Edwin M. Jacobs

Treatment of cancer with weekly intravenous 5-fluorouracil

5‐Flourouracil is usually administered by rapid intravenous injection of 15 mg/kg daily for 3 to 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 study, 129 patients with disseminated cancer were treated weekly with 5‐fluorouracil, without a loading dose, by rapid intravenous injection, beginning at 15 mg/kg/wk for 1 month, increased to 20 mg/kg/wk (if necessary) to levels producing mild toxicity or an antitumor effect. Thirty patients had an objective remission (23.3% of the total 129, and 33% of the 91 adequately treated). Thirty‐eight patients showed no drug toxicity, 75 mild, 14 moderate, and two severe toxicity. There were no drug deaths. This course enabled patients to be treated safely on an ambulatory basis.

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.

Chromosome abnormalities in human cancer. Report of a patient with chronic myelocytic leukemia and his nonleukemic monozygotic twin.

Chromosome studies were made on a 31‐year‐old man (H. vG.) with chronic myelocytic leukemia and his normal identical twin (L. vG.). Identical blood typing factors (17 tested) and similar fingerprint analyses warrant the conclusion that the twins are monozygous. Characteristic Ph1 chromosomes were found in blood and bone marrow from H.vG. before and after treatment with the colchicine analog, trimethyl colchicinic acid. During therapy the white blood count decreased from nearly 400,000/mm3 to less than 10,000/mm3. By contrast, analyses of blood and fresh bone marrow from L.vG. were consistently negative for the Ph1 chromosome. These results reinforce the postulate that the Ph1 chromosome is an acquired abnormality rather than a hereditary defect of the chromosome.

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.

Treatment of spinal cord compression in Hodgkin's disease

The management of the spinal cord lesions secondary to Hodgkins disease requires an interdisciplinary team comprising a neurosurgeon, radiation therapist, and chemotherapist to plan and supervise the treatment of the patient. Laminectomy is not always mandatory. Acute decompression can usually be achieved by chemotherapy. The advantage of using chemotherapy initially—aside from elimination of surgical morbidity—is that it permits definitive radiation therapy to be started early.

Stage III metastatic malignant testicular tumors: Treatment with intermittent and combined chemotherapy

Forty‐one patients with metastatic carcinoma of the testis were treated according to 3 cancer chemotherapeutic regimens. Thirteen responses greater than 50% and lasting more than one month were obtained. Fourteen patients received nitrogen mustard alternating with actinomycin D and 4 responses occurred. One patient is alive with no evidence of disease 5 years after treatment. Fifteen patients were treated with nitrogen mustard alternating with methotrexate and 5 responses were obtained. One patient is alive with no disease 2 years after therapy and one patient has static disease 40 months after therapy. A third patient developed hepatic metastases 18 months after complete remission of pulmonary lesions. Twelve patients received triple therapy (vincristine, an alkylating agent and methotrexate). There were 4 partial remissions lasting 4 to 5 months.

Testicular cancer: risk factors and the role of adjuvant chemotherapy.

Advances in therapeutic results due to chemotherapy in metastatic non‐seminomatous germinal cell tumors of the testes are stimulating investigations that assess the role of chemotherapy as an adjuvant to surgery and/or radiotherapy in early stages of disease. In current series, complete responses are obtained in 70–80% of patients with metastatic disease; the relapse rate is 15–20%. Toxicity is significant but acceptable. The current literature reveals that surgery and/or radiation to the periaortic lymph nodes for clinical Stage I disease results in a 2+ year disease‐free survival rate of about 90%. For clinical Stage II disease, the rate is about 50%. Patients with non‐seminomatous testicular carcinoma Stage II are at significant risk to develop distant metastases and are candidates for an intergroup protocol that randomizes patients to receive either adjuvant combination chemotherapy or combination chemotherapy at first recurrence. All patients with testicular cancer should be considered curable. This requires careful assessment and monitoring, and can best be approached in controlled clinical trials.

Combination chemotherapy and whole lung irradiation for pulmonary metastases from sarcomas and germinal cell tumors of the testis

Seven patients with sarcomas and seven with testicular carcinomas with lung metastases were treated with a multiple drug regimen of actinomycin D, cyclophosphamide, and vincristine (plus mithramycin in testicular primaries) given in a 2‐week cycle followed by a 2‐week rest period. The patients received concurrent whole lung irradiation to 1500 rads in 10 fractions. The complete response rate was 50%. Eight patients survived more than 1 year after beginning the combination therapy. Five patients have survived from 12 to 31 months, and three have been continuously free of disease. Hematologic and gastrointestinal toxicity was acceptable. Two patients developed clinical radiation pneumonitis. The results of this pilot study suggest that multiple drug therapy combined with radiation therapy to known sites of disease and to both entire lungs may offer longer complete remissions in these patients than would result from chemotherapy or radiation therapy alone.