Search

Background. The authors retrospectively analyzed 87 patients with malignant thymoma treated at M. D. Anderson Cancer Center between 1951 and 1990. The analysis examined the clinical stages, histologic types, and treatment modalities and attempted to determine if chemotherapy had an impact on survival. Methods. The patients were divided into three groups by their year of treatment and treatment modality. Patients treated between 1951 and 1975 were in Group I; patients treated between 1976 and 1980 were in Group II; and patients treated between 1981 and 1990 were in Group III. Most of the patients (18 [72%] in Group I; 16 [62%] in Group II; and 18 [50%] in Group III) had surgical resection alone or with radiotherapy. Patients with advanced-stage disease in Group I received single-agent chemotherapy, whereas patients with advanced-stage disease in Group II received a different, combination chemotherapy regimen, and those in Group III were treated primarily with cisplatin- and doxorubicin-based combination chemotherapy, e.g., the cyclophosphamide doxorubicin, and cisplatin with or without prednisone. The 17 patients treated with cisplatin with or without prednisone were separately evaluated for survival according to their response. Results. Twenty-eight patients (5 [20%] in Group I; 6 [23%] in Group II; and 17 [47%] in Group III) received chemotherapy alone or after surgery or radiotherapy. The cisplatin with or without prednisone regimen was used in 17 Group III patients for initial treatment or for relapse. The overall response rate among the patients receiving the cisplatin with or without prednisone regimen was 64%; 6 (35%) had a complete response, and 5 (29%) had a partial response. Thirty-one (36%) of the 87 total patients had 45 recurrent tumors; the lung (29%), pleura (22%), and mediastinum (18%) were the most common sites of recurrence, whereas bone was the most common distant metastatic site. The 5-year survival rate was 70% in patients with Stage I disease, 71% in patients with Stage II or III disease, and 46% in patients with Stage IV disease. The 10-year survival rate was 70% in patients with Stage I disease, 47% in patients with Stage II or III disease, and 21% in patients with Stage IV disease. Statistical analysis indicated a significant difference among the survival rates of patients with noninvasive Stage I, invasive Stage II plus III (P = 0.033), and Stage II plus III and IV tumors (P = 0.056), but not between patients with Stage II or III tumors. Patients with a major response to the cisplatin with or without prednisone regimen had a significant survival improvement compared to those with no response (P = 0.002, log-rank test). Conclusions. Because thymoma is a chemosensitive tumor and frequently recurs in patients with Stage II or greater disease, chemotherapy carries a potential survival benefit and should be incorporated into the multimodality approach to prolong disease-free survival. Cancer 1994; 73:2491-8.

Although several combinations of chemotherapeutic agents have shown some effectiveness in the treatment of non-small cell lung cancer, none is clearly superior and none is satisfactory. One agent that shows promise in the attempts to develop new chemotherapeutic protocols for lung cancer is edatrexate. This drug is similar in chemical structure to methotrexate and operates by a similar mechanism. Edatrexate inhibits the enzyme dihydrofolate reductase, which plays an important role in the synthesis of some of the bases necessary for DNA. A study was conducted to evaluate the effectiveness of a chemotherapeutic regimen which includes the standard chemotherapeutic agents cisplatin and cyclophosphamide, and the experimental agent edatrexate. Thirty-two patients with advanced stage non-small cell lung cancer participated in the clinical trial; none had received any prior chemotherapy. The study began with the treatment of 16 patients with a total dose of 800 mg per meter squared (milligrams per square meter of body area) cyclophosphamide, 80 mg per meter squared cisplatin, and 80 mg per meter squared edatrexate. This protocol yielded two complete responses and five partial responses. An additional five patients had minor responses. However, this regimen was poorly tolerated, and many patients developed a serious suppression of bone marrow and inflammation of the stomach. The dosage was therefore reduced by one-eighth for the next 16 patients. This reduction in dose resulted in a reduction in effectiveness as well; no patients in the second group achieved a complete response; four developed partial responses. Patients who developed a complete or partial response had a median survival time of 55 weeks. The median survival of the patients with a minor response was 39 weeks. The remaining patients survived a median of 27 weeks. This study suggests that edatrexate improves the response to chemotherapy with cisplatin and cyclophosphamide. However, the response curve is steep, meaning that a slight change in dose results in a significant change in effectiveness. It may be possible to improve the success of the treatment regimen if ways can be found to raise the dose while minimizing the adverse side effects of stomatitis and myelosuppression. (Consumer Summary produced by Reliance Medical Information, Inc.)

Non-small cell lung cancer (NSCLC) represents a heterogeneous group of tumors with differing responses to treatment techniques. One factor which has been shown in many other tumor types to be a predictor of prognosis is the DNA content of the tumor cells, although prognostic value has not been found for all tumor types. Cancers that have a DNA content consistent with a normal, or diploid, chromosome complement generally have a more moderate course than those with an abnormal, or aneuploid, set of chromosomes. To determine if similar considerations apply to NSCLC, 146 cases of NSCLC were examined using flow cytometry. Unlike image cytometry, in which a stained microscopic section is analyzed, flow cytometry requires that tissue be enzymatically broken up into individual cells or nuclei, which may then be automatically dropped past the cytometer's sensors. An average of 10,000 cells was evaluated for each of 146 tissue specimens. The DNA profile of the cells was interpreted in terms of its ploidy, or chromosome content, and this information was correlated not only with outcome, but with other tumor variables such as stage, differentiation, and rate of cell division. Analysis showed that among patients with squamous cell carcinoma, those with diploid cancers had a five-year survival rate of 70 percent, which was significantly higher than the 26 percent rate of patients with aneuploid tumors. Furthermore, the ploidy of the tumor did not correlate with other tumor factors, indicating that the flow cytometric measurement added new, independent information to the list of tumor features. The value of ploidy as a predictive factor did not hold if the other non-small cell lung cancers were considered together with the squamous cell carcinomas. (Consumer Summary produced by Reliance Medical Information, Inc.)