Treatment of small cell lung cancer with VP-16, vincristine, doxorubicin (Adriamycin), cyclophosphamide (EVAC), and high-dose chest radiotherapy.

Seventy-one previously untreated patients with small cell lung cancer (SCLC) received a combination of VP-16, vincristine, doxorubicin (Adriamycin), and cyclophosphamide (EVAC) repeated every three weeks. Limited-disease (LD) patients and extensive-disease (ED) patients achieving a complete response (CR) or partial response (PR) after four to six cycles of EVAC received 4,000 rads over four weeks whole-brain radiotherapy (RT) and 5,000 rads over five weeks RT to the original pulmonary primary and mediastinum. ED patients with persisting disease outside the chest after six cycles of EVAC continued chemotherapy and did not receive RT. After RT was completed, EVAC was continued for a total treatment duration of 24 months. Of 65 patients evaluable for response 76% (25 of 33) of LD patients and 34% (11 of 32) of ED patients achieved a CR prior to RT; two additional ED patients achieved a CR after RT. Median survival for all 71 patients was 48 weeks (range, one to 207 weeks); median survival for 33 LD patients was 92 weeks and for 38 ED patients it was 36 weeks. Nine of 25 LD patients and 10 of 13 ED patients have relapsed from CR. The EVAC-RT protocol is promising in view of the high CR rate and long remission duration achieved, especially among patients with LD.

Usefulness outcome in evaluating the utility of nuclear scans of the bone, brain, and liver in bronchogenic carcinoma patients.

In this study we employed the concept of the outcome audit to assess the "benefit" (in contrast to the number of positive readings) derived from 81 bone, 45 brain, and 47 liver scans, performed on 59 bronchogenic carcinoma patients. Benefit was rigorously defined and based on any outcome instrumental in the subsequent management of the patient. Clinically indicated scans were frequently found to be of benefit, while those without indications were not (88.0% vs. 12.5%). Negative scans were as useful as positive scans if clinically indicated (14.0% vs. 9.6%). Histology did not influence the likelihood of benefit. We conclude that scans obtained to evaluate a clinical abnormality are likely to be useful whether positive or negative while scans ordered without specific clinical indications are unlikely to be of management benefit.

Persistent lymphocytopenia as a diagnostic feature of bronchogenic carcinoma.

Patients with abnormalities due to bronchogenic carcinoma, noted on chest films, have decreased peripheral blood lymphocytes and increased total white cells compared to patients with benign lesions. Precision studies of 40 patients revealed that a low percentage of lymphocytes averaged over a three-week period distinguished bronchogenic carcinoma patients from patients with benign lesions with 95 percent overall accuracy. Lesions as small as 1.0 cm were correctly predicted to be malignant. Mean 8 AM plasma cortisol levels were elevated in patients with bronchogenic carcinoma and there was a negative correlation of 8 AM plasma cortisol levels with precentage of lymphocytes. Increased levels of endogenous cortisol may account for lymphocytopenia in bronchogenic carcinoma patients.

Extensive adenocarcinoma and large cell undifferentiated carcinoma of the lung treated with 5-FU, vincristine, and mitomycin C (FOMi).

Fifty-six patients with extensive (52 with TNM stage III M1 disease and four with TNM stage III M0 disease) adenocarcinoma (46 patients) and large cell undifferentiated carcinoma (ten patients) of the lung were treated with combination chemotherapy consisting of 5-FU, vincristine, and mitomycin C (FOMi). The patients had not received prior chemotherapy. The overall response rate was 41% (23 of 56 patients). Four patients achieved a complete response and 19 achieved a partial response. In 12 patients the disease was stable. Response did not vary by cell type: adenocarcinoma, 18 of 43 patients (42%); large cell carcinoma, four of ten (40%); and alveolar cell carcinoma, one of three (33%). The response varied by initial performance status. For a Karnofsky score of greater than or equal to 70%, 20 of 41 patients (49%) responded, while for a Karnofsky score of less than 70%, three of 15 patients (20%) responded (P = 0.22). Survival was improved for responding patients regardless of initial performance status. The median survival duration was 24 weeks for the entire group of patients treated with FOMi. Survival of the responders (complete response plus partial response) was significantly improved over that of patients with progressive disease (28 weeks versus 13 weeks, respectively; P = 0.002). The FOMi combination was very well-tolerated. Nausea was common, but vomiting occurred in only four of 56 patients. Thrombocytopenia, requiring a reduction in the mitomycin C dose, developed after the third treatment course in 14 patients.

Patterns of relapse in patients with small cell carcinoma of the lung treated with adriamycin-cyclophosphamide chemotherapy and radiation therapy.

Twenty-seven patients with small cell carcinoma of the lung were treated sequentially with induction chemotherapy (adriamycin and cyclophosphamide), radiation therapy (chest and whole-brain), and then maintenance chemotherapy for 2 years. Twenty responding patients were followed to relapse and patterns of recurrence were observed. This combined treatment resulted in a complete remission rate of 80% and a median survival of 565 days in limited-disease patients. Relapse overwhelmingly occurred in the chest, but patients receiving higher-dose radiation (4000-4500 rads in split-course) had a significant prolongation of time to recurrence compared to patients receiving 3000 rads in a single course of radiation (540 versus 270 days). Despite a long mean survival, only one limited-disease patient relapsed outside of the brain or chest, suggesting that chemotherapy had a good protective effect against micrometastatic disease. Three patients relapsed in the brain at 330, 450, and 520 days, suggesting that in future studies the prophylactic whole-brain radiation (3000 rads) should be intensified.

Stability of peripheral blood lymphocyte count and E-rosette forming lymphocytes in healthy adults.

Highly reproducible peripheral blood lymphocyte (PBL) count and percent E-rosette forming lymphocyte (%E-RFL) assays were developed by modifying existing procedures. PBL count assay variation was reduced by using replicate electronic white blood cell (WBC) counting and 2,000 WBC differentials. The %E-RFL assay modifications reduced variation and include the use of: (a) a capillary buffy coat isolation procedure that recovered more than 85% of the PBL without the use of chemical separation media, (b) centrifugation temperatures of 20--22 degrees C, and (c) toluidine blue staining that allowed enumeration of %E-RFL and not E-rosette forming cells, by exclusion of nonlymphoid cells. Day-to-day variation of PBL count and %E-RFL was defined by making serial determinations over a period of months. The data indicate that healthy adults maintain PBL counts and %E-RFL within narrow ranges that are specific for each individual.

In vitro effects of zinc chloride on spontaneous sheep red blood cell (e) rosette formation by lymphocytes from cancer patients and normal subjects.

The in vitro spontaneous formation of sheep red blood cell (SRBC) (E) rosettes by peripheral blood lymphocytes is altered in vitro by the addition of micro-molar quantities of zinc chloride. Appropriate concentrations of zinc chloride cause marked enhancement of rosette formation, both in normal subjects and in cancer patients with low initial E rosette values. The effect is dependent upon zinc treatment of the lymphocyte and not the SRBC. Other zinc-induced effects on E rosettes include retardation of temperature-dependent spontaneous decay, increased mechanical stability due to enhanced of "capping." The formation of EAC rosettes is not altered by the presence of zinc.

Combination chemotherapy with adriamycin (NSC-123127) and cyclophosphamide (NSC-26271) for solid tumors: a phase II trial.

One hundred and nine adult patients with metastatic carcinoma were treated at 3-4-week intervas with a combination of adriamycin (40 mg/m2 given iv on Day 1) and cyclophosphamide (200 mg/m2/day given orally in divided doses on Days 3-6). Ninety-two of 96 patients who had an adequate trial (minumum of two courses or progression of disease after one course) had follow-up observations of tumor sites and were considered evaluable for response. Overall objective response rates by tumor type were as follows: stage III or IV ovarian adenocarcinoma, 61% (14 of 23 patients); endometrial adenocarcinoma, 67% (four of six patients); cervical adenocarcinoma, 33% (one of three patients); prostatic adenocarcinoma, 18% (two of 11 patients); testicular carcinoma, 33% (one of three patients); lung carcinoma, 21% (four of 19 patients); renal adenocarcinoma, 14% (one of seven patients); gastrointestinal adenocarcinoma, 18% (two of 11 patients); melanoma, 25% (one of four patients); and miscellaneous tumors, no responses in five patients. In patients with ovarian adenocarcinoma who had not previously received any cytotoxic chemotherapy the response rate was 80% (12 of 15 patients) with 33% five of 15 patients achieving complete clinical remission. CRs in these patients have now been maintained for periods ranging from 7 to 12 months. The major toxic effects were mild to moderate leukopenia, alopecia, and nausea with vomiting. Hemorrhagic cystitis was observed in three patients. The combination of adriamycin and cyclophosphamide is an effective treatment for carcinoma of the breast (reported elsewhere), ovary, and endometrium and should be considered for initial chemotherapy in patients with these tumors. Further investigations of its use for melanoma and carcinoma of the lung, prostate, kidney, and gastrointestinal tract are also warranted.

Combination chemotherapy with methyl-CCNU (NSC-95441), cyclophosphamide (NSC-26271), vincristine (NSC-67574), methotrexate (NSC-740), and bleomycin (NSC-125066) in advanced bronchogenic carcinoma.

Forty consecutive eligible patients with advanced bronchogenic carcinoma and no prior chemotherapy were treated with a 5-drug combination of methyl-CCNU, cyclophosphamide, methotrexate, vincristine, and bleomycin. Of the 36 patients who completed at least one 6-week course of treatment and were considered evaluable, 4 (11%) had partial tumor response. Response by cell type was as follows: 2(14%) of 14 patients with squamous cell carcinoma, 2(18%) of 11 with oat cell carcinoma, and none of 11 with adenocarcinoma. Toxicity in the group of 36 evaluable patients consisted of nausea and vomiting in 24 patients (67%), severe leukopenia (white blood cell count less than 1000 cells/-mm3) in 7 patients (19%), severe thrombocytopenia (platelet count less than 100,000 platelets/mm3) in 14 patients (39%), and bleomycin pulmonary toxicity in 2 patients (6%). This combination does not appear to be more effective than single-agent chemotherapy for bronchogenic carcinoma.