Paclitaxel: a radiation sensitizer of human cervical cancer cells.

Paclitaxel is an exciting chemotherapeutic agent active in a variety of malignant tumors. This study was designed to explore the radiosensitizing potential of paclitaxel in human cervical cancer cell lines. The cell lines ME180, SiHa, and MS751 were evaluated. Experiments were performed in the proliferative phase of growth. Paclitaxel doses were treated at 0.01x, 0.02x, 0.03x, 0.04x, and 0.05x peak plasma concentration (PPC) in ME180 and 0.001x, 0.002x, 0.003x, 0.004x, and 0.005x PPC in SiHa and MS751. Radiation (RT) doses of cobalt-60 were 0, 2, 4, 6, 8, and 10 Gy. In the combination group RT was given 48 hr after paclitaxel treatment. To allow for median effect analyses, combination doses were kept at a fixed ratio: 0.01x/2 Gy, 0.02x/4 Gy, 0.03x/6 Gy, 0.04x/8 Gy, and 0.05x/10 Gy for ME180 and 0.001x/2 Gy, 0.002x/4 Gy, 0.003x/6 Gy, 0.004x/8 Gy, and 0.005x/10 Gy in MS-751 and SiHa. Adenosine triphosphate bioluminescence was performed on Day 7 after treatment and compared to untreated controls. Dose-response data were fit to the linear quadratic model and mean inactivation dose D was calculated. Data analysis with t test was performed. The median effect principle was used to evaluate the nature of the interaction between the two therapeutic modalities. Paclitaxel increased radiation cytotoxicity in all three cell lines. Mean inactivation D values for RT versus combination were 6.70 (+/- 0.15) and 4.33 (+/- 0.43) (P = 0.004) in ME180, 6.08 (+/- 0.70) and 4.54 (+/- 0.093) (P = 0.033) in MS751, and 7.03 (+/- 0.46) and 5.97 (+/- 0.51) (P = 0.034) in SiHa. The interaction of paclitaxel and RT was found to be supraadditive in ME180 and SiHa and subadditive in MS751. We conclude that paclitaxel has modest radiation-sensitizing effects in cervical cancer cell lines and that further clinical trials should be considered.

National survey of ovarian carcinoma XII. Epithelial ovarian malignancies in women less than or equal to 25 years of age.

BACKGROUND: Epithelial ovarian carcinoma in women less than or equal to 25 years of age is a rare entity. This study used the database of the National Survey of Ovarian Carcinoma to analyze the disease and survival in women less than or equal to 25 years of age. METHODS: Tumor registries of 1230 hospitals were asked to enter the first 25 patients with histologically confirmed ovarian carcinoma from January 1 to December 31, 1983 and from January 1 to December 31, 1988. Data for a total of 12,136 patients were collected. Survival analysis and long-term evaluations were available on patients diagnosed with cancer in 1983. Chi-square analysis was used to compare the frequencies of operations performed in 1983 and 1988. RESULTS: Of 12,136 patients with epithelial ovarian carcinoma, 135 (1.1%) were less than or equal to 25 years of age. The majority of patients had early disease with the following distributions: stage I, 58.5%; stage II, 8.9%; stages III and IV, 28.9%. More patients had early-grade lesions with the following distributions: borderline, 21.5%; Grade 1, 27.4%; Grade 2, 11.1%; Grade 3, 6.7%; and unknown grade, 33.3%. Optimal cytoreduction was achieved in 77% of patients. During the 5-year study period, there was a significant change in the patterns of care toward more conservative surgery. In particular, unilateral salpingooophorectomy increased significantly from 38.2 to 59.7% (P = 0.0237), whereas hysterectomy decreased proportionally from 54.4 to 29.9% (P = 0.0039). The overall 5-year survival rate was 87.3% with the following divisions: stage I, 96.7%; stage II, 90.0%; stage III, 78.5%; and stage IV, 76.4%. Regarding histologic grade, 5-year survival rates were: borderline, 91.6%; Grade 1, 93.7%; Grade 2, 85.7%; Grade 3, 33.3%. CONCLUSION: Young patients with epithelial ovarian carcinoma appeared to have favorable stage and histologic grade. These factors combined with good performance status and optimal cytoreduction resulted in improved survival from cancer.