Does vinblastine add to the potency of alpha interferon in the treatment of renal cell carcinoma?

The combination of alpha interferon and vinblastine has been reported to yield a response rate of 30-40% in previously untreated patients with metastatic renal cell carcinoma. This combination was given to nine patients with advanced metastatic renal carcinoma after they failed or relapsed on alpha-interferon alone, to attempt to evaluate the role of vinblastine in this combination. Neither complete nor partial response was observed. Two patients had disease stabilization for two and seven months. Our preliminary results suggest that vinblastine did not add to the efficacy of interferon in this group of patients.

Femoral and skull metastasis with hypercalcemia: occurrence with esophageal carcinoma without dysphagia.

The most common initial symptom of esophageal neoplasm is dysphagia. When metastasis occurs, it is most frequent to neighboring lymph nodes, mediastinum, or viscera, eg, the lungs and liver, and only infrequently to bones. Even less frequently do these metastases occur with hypercalcemia. A 59-year-old woman was initially seen with hypercalcemia and bone pain in the hip and leg, which subsequently proved to be the site of metastatic spread secondary to squamous cell carcinoma of the esophagus. Until her death, approximately four months after the diagnosis, she never experienced dysphagia, epigastric or substernal pain, or regurgitation.

Vinblastine, cyclophosphamide and 5-fluorouracil (VEF) combination chemotherapy for metastatic hypernephroma.

10 evaluable patients with metastatic hypernephroma received vinblastine (6 mg/m2, i.v., on days 1 and 8), cyclophosphamide (100 mg/m2, p.o., on days 1-14), and 5-fluorouracil (600 mg/m2, i.v., on days 1 and 8), cycled every 29 days. 7 of the patients also received dexamethasone (16 mg/day, p.o), shortly before or during chemotherapy, in an attempt to improve their clinical status. No complete or partial responses were seen. 5 pairs (50%) remained stable (median duration, 4.5 months; medium survival, 6.5 months), and the remaining 5 patients progressed. A subjective response was observed in all stable patients, who also received dexamethasone. The side-effects of VEF chemotherapy were mild: 2/10 patients developed leukopenia (WBC below 3,000), 3/10 patients manifested thrombocytopenia (platelets below 100,000), and 3/10 patients alopecia.

Paraneoplastic syndromes: unusual manifestations of malignant disease.

This monograph has attempted to summarize in a general fashion the ever-enlarging spectrum of the paraneoplastic syndromes. Recognition of their presence at times can lead to the earlier diagnosis of an underlying malignancy. In many instances, palliative therapy or correction of the syndrome may produce relief from the multiplicity of symptoms that develop. The syndromes may be readily apparent or subtle in their onset. Some are life threatening. Prompt recognition and institution of therapy are essential in those instances. The paraneoplastic syndromes usually are categorized by organ system, target organ involved or, where possible, by mediating factors. A careful study of these symptom complexes may lead to better methods of detecting cancer, as well as to a better understanding of its etiology and prevention in the human.

EST 0469B--comparison of high- and low-dose cyclophosphamide in human lung cancer.

A controlled trial of high-intermittent vs low-chronic dose cyclophosphamide in human lung cancer failed to show the benefits reported in noncontrolled trials. There were no differences in toxicity observed.

Methotrexate compared with placebo in lung cancer.

Two hundred thirty-nine patients with microscopically proven, inoperable bronchogenic carcinoma were allocated at random to receive twice weekly I.M. injections of either methotrexate at "high dose" of 0.06 mg/kg/dose or methotrexate at "low dose" of 0.2 mg/kg or visually indistinguishable placebo in the same volume of 0.1 ml/kg for four months. Twelve patients were invalidated for procedural reasons. Objective response (greater than or equal to 50% tumor regression) was dose-related with 21% of 48 patients with measurable disease on high -ose, 11% of 37 patients on low dose, and 6% of 32 patients on placebo. Corresponding response rates for epidermoid carcinoma were 35% of 23 patients, 9% of 11 patients, and 0 of 13 patients. Responders in the two treatment groups had a three to four fold increase of median survival (p less than .05). Non-responders on high and low dose methotrexate lived as long as patients on placebo. Leukopenic patients in all three treatment groups lived substantially longer than patients without leukopenia less than 4,500/mm3, irrespective of presence or absence of objective response. All three regimens were well tolerated. None of the patients had life-threatening toxicity. It is concluded that methotrexate at "high dose" is a potentially useful drug for temporary palliation of epidermoid carcinoma of the lung.

Combination chemotherapy of the malignant lymphomas: a controlled clinical trial.

The Eastern Cooperative Oncology Group has studied 113 patients with generalized progressive malignant lymphomas in a randomized clinical trial. Pathologic diagnosis was subclassified by cell type and nodal pattern by The Pathology Panel for Lymphome Clinical Trials. Patients were randomly assigned treatment with either cyclophosphamide (C), vincristine (O), and prednisone (P) (COP) or CO without prednisone. Initial treatment was given for 8 weeks and further randomization of responders to observation or additional chemotherapy was carried out. A significant difference in complete remission rate between treatments was shown: with COP, 43%, and with CO, 17%, indicating an important role for prednisone in inducing CR. COP was also associated with longer remission durations and improved survival. Complete remission following initial chemotherapy is also associated with longer duration of disease-free time and survival. The initial pathologic cell types and nodal pattern also strongly influence survival. Extended "maintainence" CO treatment improved disease-free remission duration, but not survival.

A phase I study of 5-azacytidine (NSC-102816).

5-Azacytidine was administered daily to 12 patients in a five-day schedule and to 15 patients in a weekly schedule as part of a phase I trial. The daily dose ranged from 50 mg/m2 to 158 mg/m2 and the weekly dose, from 200 mg/m2 to 633 mg/m2. The maximum total dose was 2000 mg in the daily schedule and 3775 mg in the weekly schedule. The major toxicity was gastrointestinal, with nausea and vomiting occurring in all patients in this study. Myelosuppression was less frequently encountered and appeared to be related to the increase in 5-azacytidine dose. Patients receiving 5-azacytidine in a weekly schedule of administration appeared to tolerate the drug better and to be more willing to continue their therapy.

Comparative evaluation of combined radiation-chlorambucil treatment of ovarian carcinomatosis.

In a study conducted by the Eastern Cooperative Oncology Group, 51 evaluable women with advanced ovarian carcinoma were randomized to either abdominal radiation therapy alone, chlorambucil alone, or to a combination of radiation therapy and chlorambucil by members of the Eastern Cooperative Oncology Group. Provision was made for crossover therapy for patients who were nonresponders to a single modality of treatment. Parameters followed included objective and subjective response rates and patient survival. The total response rate was 51%, with no significant difference among the three treatment regimens. Regarding survival, radiation therapy alone was significantly superior to the other regimens, with an average survival of 94.9 weeks. Best results were obtained in patients with normal performance status; for this group, radiation therapy alone offered the best chance for prolonged survival.

Clinical studies of 5-fluorouracil + premarin in the treatment of breast cancer.

Sixty patients with metastatic or primary inoperable breast cancer not suitable for hormone alteration therapy were blindly randomized between weekly 5-fluorouracil, intravenously, and daily physiologic doses of conjugated estrogens by mouth against weekly 5-fluorouracil, intravenously, and placebo. There was no difference in the survival or the effect on the tumor in the two groups. Numerous factors were analyzed as to their effect on the course of the disease. The number of organ sites of tumor involvement, age of the host, and previous treatment for the disseminated disease were not shown to influence the survival or the results of therapy of either group. However, the duration of the clinical cancer-free period from primary treatment to recurrence, the sites of organ involvement, and the performance status of the patients at the time of entry into the study significantly did influence the survival. There is no evidence in this study that physiologic doses of conjugated estrogens deleteriously influenced the course of the disease.

Clinical evaluation of two weekly dose schedules of 'IC-140'. 4-N, N-bis (2-Chloroethyl) amino phenyl N (P-carboxyphenyl) carbamate, in the treatmentment of solid tumors 1,2.

53 patients with intractable malignant diseases that were treated with a new alkylating agent, 4-N,N-bis (2-chloroethyl) amino phenyl N (P-carboxyphenyl) carbanate, also knows as 'IC-140' were evaluated. The records of an additional 41 patients entered on this study could not be assessed from the standpoint of toxicity. At the dose level of 150 mg/m2/week, severe leukopenia (less than 2,000) and thrombocytopenia ( less than 75,000) were encountered in 23 of 34 patients. On the other hand, at the 100 mg/m2/week dose level, the severe toxicity was reduced to 8 out of 19 patients. Tumor response was evaluated in 43 patients. The overall response was 23% (29% at the 150 mg/m2, 13% at the 100 mg/m2) and the duration of the response varied from 3 to 32 weeks with a mean duration of 13 weeks. Responses were noted in patients with ovarian, renal, lung, hepatic, breast carcinomas and lymphosarcoma.