Robert C. Young

Prognostic factors for high-risk early-stage epithelial ovarian cancer: a Gynecologic Oncology Group study.

The purpose was to identify the factors predictive of recurrence and survival in patients with high‐risk (stage I, grade 3; stage IC, stage II, or clear cell) epithelial ovarian cancer after adjuvant therapy.

Associations between p53 overexpression and multiple measures of clinical outcome in high-risk, early stage or suboptimally-resected, advanced stage epithelial ovarian cancers: A Gynecologic Oncology Group study

OBJECTIVE The Gynecologic Oncology Group (GOG) performed a detailed analysis of p53 overexpression in previously-untreated women with invasive early or advanced stage epithelial ovarian cancer (EOC). METHODS Women were eligible for the study if they provided a tumor block for translational research and participated in either GOG-157, a randomized phase III trial of three versus (vs.) six cycles of paclitaxel+carboplatin in high-risk, early stage EOC, or GOG-111, a randomized phase III trial of cyclophosphamide+cisplatin vs. paclitaxel+cisplatin in suboptimally-resected, advanced stage EOC. The N-terminal DO-7 p53 antibody was used to examine the expression of the major normal and mutant p53-isoforms. p53 overexpression was defined as >or=10% tumor cells exhibiting nuclear staining. RESULTS p53 was overexpressed in 51% (73/143) and 66% (90/136) of cases in the GOG-157 and GOG-111 cohorts, respectively. In the GOG-157 cohort, p53 overexpression was not associated with any clinical characteristics or overall survival (OS) but was associated with worse progression-free survival (PFS) (logrank test: p=0.013; unadjusted Cox modeling: p=0.015). In the GOG-111 cohort, p53 overexpression was associated with GOG performance status (p=0.018) and grade (p=0.003), but not with age, stage, cell type or with tumor response and disease status after primary chemotherapy, PFS or OS. Adjusted Cox regression modeling demonstrated that p53 overexpression was not an independent prognostic factor for PFS or OS in either cohort. CONCLUSIONS p53 overexpression assessed by DO-7 immunostaining is common in early and advanced stage EOC, but has limited prognostic value in women treated with surgical staging and platinum-based combination chemotherapy.

Mechanisms to improve chemotherapy effectiveness.

Although many effective anti‐cancer agents are now available, their curative potential is compromised by a variety of problems related to tumor sensitivity, drug access, and pharmacokinetics. Central to the problem of inadequate chemotherapy is drug resistance. Drug resistance may be intrinsic, acquired, or induced, and it may develop to one drug or it may occur simultaneously to multiple agents (pleiotropic). Substantial progress has been made in our understanding of the mechanisms of drug resistance and techniques for overcoming that resistance. New evidence has emerged that highlights the importance of dose intensity in achieving successful drug treatment outcomes. Retrospective analysis of studies in breast, ovarian, colon cancer, and lymphoma suggest that new studies designed to optimize dose intensity may yield improved results. Several prospective trials have now corroborated the retrospectively derived importance of dose intensity as an independent factor in achieving improved survival. Finally, new techniques for drug delivery offer considerable promise. Chemotherapy by regional infusion and perfusion, implantable drug delivery systems, and continuous infusion of chemotherapy are unique novel techniques that may improve the efficacy of presently available chemotherapeutic agents even as new agents are developed.

Early ovarian cancer: a review of its genetic and biologic factors, detection, and treatment.

Early-stage ovarian carcinoma requires comprehensive surgical staging; reexploration for patients who had suboptimal initial surgery would indicate an apparent early ovarian carcinoma. After proper surgery, patients can be subdivided into a high- or low-risk group, and treatment options then can be discussed with the patient. Patients in the low-risk category can be followed up expectantly without any form of adjuvant therapy. Patients in the high-risk category, however, should be encouraged to participate in randomized clinical trials, because it is unclear at the current time which combination of chemotherapy and how many treatments should be used. A platinum-based paclitaxel regimen probably should be used, although the relative merits of carboplatin and cisplatin and the appropriate schedule for taxol (1 hour vs. 3 hours vs. 24 hours vs. 96 hours) are yet unknown. It is hoped that clinicians will continue to encourage patients to participate in randomized clinical trials so that optimal therapy for early ovarian cancer can be established.

Stage II carcinoma of the ovary: An analysis of survival after comprehensive surgical staging and adjuvant therapy

Ninety-three women with FIGO stage II epithelial ovarian carcinoma underwent comprehensive surgical staging and were randomized prospectively to therapy consisting of either intraperitoneal radioactive phosphorus or oral melphalan. No patient had gross residual disease at the time of randomization. Ten of the forty-five women treated with melphalan experienced severe bone marrow depression at some time during therapy and two women expired from leukemia. Four of the forty-eight women treated with intraperitoneal phosphorus required surgical reexploration for intestinal obstruction or bowel injury. Twenty-one women died of their disease. Survival was not statistically different between the two treatment arms. The 5-year actuarial survival was 78%.

The association between timing of initiation of adjuvant therapy and the survival of early stage ovarian cancer patients – An analysis of NRG Oncology/Gynecologic Oncology Group trials

OBJECTIVES To determine the association between timing of adjuvant therapy initiation and survival of early stage ovarian cancer patients. METHODS Data were obtained from women who underwent primary surgical staging followed by adjuvant therapy from two Gynecologic Oncology Group trials (protocols # 95 and 157). Kaplan-Meier estimates and Cox proportional hazards model adjusted for covariates were used for analyses. RESULTS Of 497 stage I-II epithelial ovarian cancer patients, the median time between surgery and initiation of adjuvant therapy was 23days (25th-75th%: 12-33days). The time interval from surgery to initiation of adjuvant therapy was categorized into three groups: <2weeks, 2-4weeks, and >4weeks. The corresponding 5-year recurrence-free survival rates were 72.8%, 73.9%, and 79.5% (p=0.62). The 5-year overall survival rates were 79.4%, 81.9%, and 82.8%, respectively (p=0.51; p=0.33 - global test). As compared to <2weeks, the hazard ratio for recurrence-free survival was 0.90 (95%CI=0.59-1.37) for 2-4weeks and 0.72 (95%CI=0.46-1.13) for >4weeks. Age, stage, grade, and cytology were important prognostic factors. CONCLUSIONS Timing of adjuvant therapy initiation was not associated with survival in early stage epithelial ovarian cancer patients.

The sounds of silence.

No news about cancer prevention is good news.