PURPOSE: To evaluate the relative effect of percent maximal cytoreductive surgery and other prognostic variables on survival among cohorts of patients with advanced-stage ovarian carcinoma treated with platinum-based chemotherapy. MATERIALS AND METHODS: Eighty-one cohorts of patients with stage III or IV ovarian carcinoma (6,885 patients) were identified from articles in MEDLINE (1989 through 1998). Linear regression models, with weighted correlation calculations, were used to assess the effects on log median survival time of the proportion of each cohort undergoing maximal cytoreduction, dose-intensity of the platinum compound administered, proportion of patients with stage IV disease, median age, and year of publication. RESULTS: There was a statistically significant positive correlation between percent maximal cytoreduction and log median survival time, and this correlation remained significant after controlling for all other variables (P < .001). Each 10% increase in maximal cytoreduction was associat...

Survival Effect of Maximal Cytoreductive Surgery for Advanced Ovarian Carcinoma During the Platinum Era: A Meta-Analysis

Studies have shown that in the curative setting patients with cancer receiving chemotherapy at higher relative dose intensity (RDI) had better clinical outcomes than those receiving treatment at lower RDI. However, the impact of RDI in advanced/metastatic disease remains unclear. A review of the literature was performed to evaluate the relationship between RDI and survival in patients with metastatic lung, breast, or ovarian cancer receiving chemotherapy. Few studies attempted to specifically associate RDI with survival in a systematic way. Findings from studies that analyzed overall survival with a prespecified RDI threshold support the emerging perception that maintaining an RDI≥85% has a favorable impact on survival. Nonetheless, these studies were limited by their retrospective nature. More studies are needed to further evaluate the impact of maintaining planned chemotherapy dose intensity on outcomes in metastatic solid tumors.

A review of relative dose intensity and survival in patients with metastatic solid tumors

Purpose: This Phase I study was undertaken to define the toxicity, pharmacodynamics, and maximum tolerated dose of the combination of R115777, a farnesyl transferase inhibitor, with gemcitabine and cisplatin in patients with advanced solid tumors. Patients and Methods: Thirty patients with solid tumors received a median of 2.5 cycles (range 1–30+) through five dose levels. R115777 was administered p.o. twice daily for 14 days. Gemcitabine was infused 15 min after the ingestion of R115777 on days 1 and 8. Cisplatin was administered starting 30 min after completion of the gemcitabine infusion on day 1. Cycles were repeated every 21 days. Toxicities were graded by the National Cancer Institute Common Toxicity Criteria and recorded as maximum grade per patient for each treatment cycle. At the maximum tolerated dose, accumulation of prelamin A in buccal mucosa cells of patients was evaluated as a marker of farnesyl transferase inhibition by R115777. Results: Neutropenia and thrombocytopenia were the most common toxicities. Dose-limiting toxicity in cycle 1 was myelosuppression with thrombocytopenia alone (4 patients), neutropenia alone (1 patient), or a combination of both (3 patients). Common nonhematologic toxicities were anorexia, rash, nausea, vomiting, and fatigue, none of which was dose limiting in the first cycle. At the maximum tolerated dose, defined as R115777 300 mg twice daily p.o., 1000 mg/m 2 gemcitabine, and 75 mg/m 2 cisplatin, inhibition of prelamin A farnesylation in buccal mucosa cells of patients was demonstrated, confirming that R115777 inhibits protein farnesylation in vivo . Nine objective responses (one complete response and eight partial responses) were documented in 27 evaluable patients. Conclusion: The combination of R115777 with gemcitabine and cisplatin was well tolerated and showed evidence of antitumor activity. The maximum tolerated dose of R115777 successfully inhibits farnesyltransferase in patients in vivo . This combination warrants further evaluation in a number of tumor types.

https://clincancerres.aacrjournals.org/content/clincanres/9/7/2520.full.pdf

A Phase I trial of the farnesyl protein transferase inhibitor R115777 in combination with gemcitabine and cisplatin in patients with advanced cancer.

Optimal dose reduction of FOLFIRINOX for preserving tumour response in advanced pancreatic cancer: Using cumulative relative dose intensity

The survival benefit of neoadjuvant chemotherapy (NAC) was assessed in patients with FIGO stage III or IV ovarian cancer, and the prognostic value of various therapeutic factors was determined. In patients treated for stage III or IV ovarian malignancies at the Department of Obstetrics and Gynecology of Nagoya University or related institutions between 1987 and 1996, 119 had a histologic diagnosis of serous cystadenocarcinoma. For this group, the long-term outcome was compared between 96 patients receiving conventional adjuvant chemotherapy following standard surgery and 23 patients treated with NAC, both followed by a second cytoreductive surgery. In a total of 29 patients with all histologic types of malignancy, the tumor response to NAC and survival were analyzed on the basis of histology, chemotherapy regimen, residual tumor size after the second cytoreductive operation, and the dose intensity of cisplatin. The long-term outcome (5-year survival rate) was better in patients treated with conventional adjuvant chemotherapy than in patients receiving NAC, although the difference was not significant. Overall survival did not differ significantly in relation to tumor histology or chemotherapy regimen. With respect to residual tumor size after the second surgery, patients with a residual tumor 2 cm. A better prognosis was also associated with a higher dose intensity of cisplatin, and patients treated at >or = 18 mg/m(2)/week survived significantly longer than those receiving <18 mg/m(2)/week.

https://ijgc.bmj.com/content/ijgc/13/5/587.full.pdf

Neoadjuvant chemotherapy for FIGO stage III or IV ovarian cancer: Survival benefit and prognostic factors.

High-dose platinum versus standard dose in advanced ovarian carcinoma: a randomized trial from the Gynecologic Cooperative Group of the French Comprehensive Cancer Centers (FNCLCC).

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High-dose platinum versus standard dose in advanced ovarian carcinoma: a randomized trial from the Gynecologic Cooperative Group of the French Comprehensive Cancer Centers (FNCLCC).