Brief intensive chemotherapy for metastatic non-small-cell lung cancer: a phase II study of the weekly CODE regimen.

Fifty-three patients, 17 with stage IIIB and 36 with stage IV non-small-cell lung cancer, were given CODE (cisplatin, vincristine, doxorubicin, and etoposide) plus antibiotic prophylaxis and an antiemetic regimen in an intensive chemotherapy program emphasizing weekly treatment and a planned brief duration (9-12 weeks); for 45 of these patients, the CODE program also included antifungal prophylaxis and supportive corticosteroids. Of the total study population, 33 patients (62%) responded to treatment, including five (9%) with complete response. The median survival for the entire group was 42 weeks (55 weeks for those with stage IIIB and 39 weeks for those with stage IV). More than 40% were alive at 1 year. Comparison of granulocyte counts of patients receiving prednisone with those of the subgroup to whom no corticosteroids were given showed less granulocytopenia for those receiving prednisone. Use of prednisone thus allowed improved delivery of myelosuppressive drugs. CODE was halted in nine patients because of disease progression. Although more constitutional side effects are associated with weekly chemotherapy than with standard chemotherapy, only 12 of the remaining 44 patients (27%) failed to receive at least 9 weeks of treatment. Serious toxicity was uncommon: There were no treatment-related deaths and only three episodes of neutropenia with fever. CODE is a novel treatment for non-small-cell lung cancer that this pilot study provided entirely in an outpatient setting over a 9-12 week period with an acceptable incidence of toxicity and a promising level of efficacy. Additional testing and comparison with other regimens or supportive care alone are warranted.

Intensive weekly chemotherapy for the treatment of extensive-stage small-cell lung cancer.

The regimen of cisplatin, vincristine, doxorubicin, and etoposide (CODE) was designed to double the dose intensity of these drugs in comparison with a standard regimen (alternating cyclophosphamide, doxorubicin, and vincristine [CAV] and etoposide-cisplatin [EP]) for extensive-stage small-cell lung cancer (SCLC). The dose intensity was increased by more frequent treatments rather than by increasing the dose size. The structure of this outpatient protocol includes weekly administration of chemotherapy, alternation of myelosuppressive and nonmyelosuppressive treatments, supportive corticosteroids, gastroprotective agents, and prophylactic antibiotics. Although the duration of chemotherapy was brief (9 to 12 weeks), the total cumulative doses of drugs delivered were similar to the standard regimen. Patients with no residual disease outside the chest after chemotherapy received thoracic irradiation, and patients with complete responses (CRs) received prophylactic cranial irradiation. Eligible extensive-stage SCLC patients were ambulatory, younger than 66 years of age, and free of brain metastasis. Forty-eight extensive-stage SCLC patients were treated. Forty-five (94%) responded to chemotherapy, with 19 (40%) attaining CR. After consolidative thoracic irradiation, the CR rate was 56%. The median time to progression was 43 weeks, and the median survival was 61 weeks. The 2-year survival rate was 30%. The most common site of first relapse was brain (38%). Although two patients (4%) died of toxicity, overall toxicity was acceptable for an outpatient regimen. We conclude that the CODE regimen reliably produces palliative remissions for selected extensive-stage SCLC patients, and it may be associated with durable remissions for some patients. The results of this pilot study are sufficiently promising to justify a phase III trial of CODE versus standard (alternating CAV and EP) chemotherapy.

Quality of life, appetite, and weight change in patients receiving dose-intensive chemotherapy.

Quality of life was assessed by self-report questionnaires in 30 patients receiving dose-intensive chemotherapy for either non-small-cell lung cancer (20 patients) or recurrent head and neck cancer (10 patients). Megestrol acetate was given daily to try to improve appetite and prevent the weight loss usually associated with this chemotherapy. Appetite did not change significantly overall during the first 4 weeks of chemotherapy, but it did improve in those patients still receiving chemotherapy at 8 weeks. Changes in global quality of life were significantly correlated with changes in appetite, fatigue, energy level, and physical function. Thus, these parameters may have more relevance to patients' perceptions of quality of life than does weight change, and should be used more frequently as endpoints in studies of supportive care and palliative treatment of patients with cancer.

Phase II trial of megestrol in the supportive care of patients receiving dose-intensive chemotherapy.

Megestrol acetate was given daily to lung cancer patients undergoing therapy with CODE and to recurrent head and neck cancer patients receiving DEB/M in an attempt to prevent weight loss. The outcomes in this study were compared with the same outcomes in similar groups of patients treated with the same chemotherapy regimens, but in which prednisone was used as the main supportive drug along with co-trimoxazole, ketoconazole, and either cimetidine or sucralfate. Weight loss was less pronounced in the current patients than in the previous ones. Nevertheless, there were several factors that led us to conclude that megestrol is not an adequate substitute for prednisone in patients receiving this kind of chemotherapy.

Familial hemophagocytic lymphohistiocytosis (FHLH) in Israel. I. Description of 11 patients of Iranian-Iraqi origin and review of the literature.

Eleven patients with familial hemophagocytic lymphohistiocytosis (FHLH) are described. They all belonged to four Jewish families of Iranian and Iraqi origin. Parental consanguinity was found in three families. The age of onset of disease ranged from 6 weeks to 36 months. All patients had fever, wasting, and enlargement of the liver and spleen. In addition, lymph-node enlargement and neurologic complications were common. The most consistent laboratory findings were pancytopenia, atypical lymphomonocytoid cells in the peripheral blood, abnormal liver function test results, and increased cerebrospinal fluid protein. The course was fatal in all patients. Nine of the 11 patients died within 2 weeks to 3 months of presentation, and 2 patients achieved temporary remissions but died of disease within 8 and 24 months, respectively. Response to antibiotic therapy or to the administration of corticosteroids and cytotoxic drugs was unimpressive. Pancytopenia complicated by sepsis or bleeding, hepatic failure, or encephalopathy were the terminal events. This report draws attention to the existence of FHLH in Jews of Iranian-Iraqi origin in whom parental consanguinity is very common.

Cervical intraepithelial neoplasia in female prisoners in British Columbia.

The annual incidence rates of cervical intraepithelial neoplasia (CIN), grades I to III, from 1975 to 1983 among 2440 prisoners in British Columbia for whom a history of screening by means of the Papanicolaou test was available were two to three times higher than the expected rates in the general female population of British Columbia. The rates among the prisoners from 1970 to 1984, although small, increased with a trend similar to that in the general population. Despite increases in the general population we conclude that prisoners are still at high risk for CIN.