Robert V. O'Toole

Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer

BACKGROUND Intravenous platinum-based chemotherapy is the standard primary therapy for advanced ovarian cancer. We conducted a phase 3 trial to compare the effects of intraperitoneal and intravenous cisplatin on the survival of women with previously untreated, stage III, epithelial ovarian cancer. METHODS The patients underwent an initial exploratory laparotomy and resection of all tumor masses larger than 2 cm. Within four weeks after surgery, six courses of intravenous cyclophosphamide (600 mg per square meter of body-surface area per course) plus either intraperitoneal cisplatin (100 mg per square meter) or intravenous cisplatin (100 mg per square meter) were administered at three-week intervals. RESULTS Of 654 randomized patients, 546 were eligible for the study. The estimated median survival was significantly longer in the group receiving intraperitoneal cisplatin (49 months; 95 percent confidence interval, 42 to 56) than in the group receiving intravenous cisplatin (41 months; 95 percent confidence interval, 34 to 47). The risk of death was lower in the intraperitoneal group than in the intravenous group (hazard ratio, 0.76; 95 percent confidence interval, 0.61 to 0.96; P = 0.02). Moderate-to-severe tinnitus, clinical hearing loss, and neuromuscular toxic effects were significantly more frequent in the intravenous group. CONCLUSIONS As compared with intravenous cisplatin, intraperitoneal cisplatin significantly improves survival and has significantly fewer toxic effects in patients with stage III ovarian cancer and residual tumor masses of 2 cm or less.

Improved therapeutic index of carboplatin plus cyclophosphamide versus cisplatin plus cyclophosphamide: final report by the Southwest Oncology Group of a phase III randomized trial in stages III and IV ovarian cancer.

PURPOSE To compare cisplatin-cyclophosphamide versus carboplatin-cyclophosphamide as primary chemotherapy for stage III (suboptimal) and stage IV ovarian cancer. PATIENTS AND METHODS Three hundred forty-two patients were randomly assigned to treatment with six courses of intravenous (i.v.) cisplatin 100 mg/m2 plus i.v. cyclophosphamide 600 mg/m2, or i.v. carboplatin 300 mg/m2 plus i.v. cyclophosphamide 600 mg/m2. RESULTS The estimated median survivals were 17.4 and 20.0 months for the cisplatin and carboplatin study arms, respectively. The null hypothesis of a 30% survival superiority with the cisplatin arm was rejected at the P = .02 level. Clinical response rates were 52% for the cisplatin arm and 61% for the carboplatin arm. Pathologic complete response rates were similar for both study arms. There was less thrombocytopenia on the cisplatin arm (P less than .001); however, there was less nausea and emesis (P less than or equal to .001 for courses 1 to 5), renal toxicity (P less than .001), anemia (P = .01), hearing loss (P less than .001), tinnitus (P = .01), neuromuscular toxicities (P = .001), and alopecia (P less than .001) on the carboplatin arm. CONCLUSION Carboplatin-cyclophosphamide proved to have a significantly better therapeutic index than cisplatin-cyclophosphamide in patients with stage III (suboptimal) and stage IV ovarian cancer.

DNA ploidy and prostate-specific antigen as prognostic factors in clinically resectable prostate cancer.

Prostate‐specific antigen (PSA) and DNA ploidy as measured by flow cytometry were compared with conventional prognostic indicators in 112 patients who underwent radical prostatectomy for clinically resectable prostate cancer. The variables examined included age, race, prostatic acid phosphatase (PAP), Gleason score of the radical prostatectomy specimen, and pathologic stage. No significant relationships were found between DNA ploidy and age, mean PAP value, and absolute PAP value. Of the 112 patients, 65 (58.0%) had disease limited to the prostate (pathologic Stages A and B); 47 (42.0%) had extraprostatic disease (pathologic Stages C and D1). The stage was related to the Gleason score (P < 0.0001) where extraprostatic disease was associated with a Gleason score of 6 to 10. Nineteen (17.0%) patients had aneuploid tumors, and 93 (83.0%) had diploid tumors. DNA ploidy significantly correlated with pathologic stage (P = 0.04); aneuploidy was identified more frequently in patients with Stages C and D1 tumors. Aneuploid tumors occurred more frequently than diploid tumors in patients with a Gleason score of 6 to 10 (P = 0.034). Mean PSA values were higher in patients with aneuploid tumors (P = 0.078), extraprostatic neoplasms (P = 0.00001), and cancers with a Gleason score of 6 to 10 (P = 0.0004). Furthermore, PSA values greater than 10.0 ng/ml were associated with extraprostatic disease and a Gleason score of 6 to 10 (P < 0.05 and P < 0.001, respectively). Significant racial differences were found with respect to DNA ploidy, mean DNA indices, and mean PSA values. The 18 black patients had more DNA aneuploid tumors (P = 0.043), a higher mean DNA index (P = 0.017), and a higher mean PSA value (P = 0.043) than the 94 white patients. Both PSA and DNA ploidy analysis by flow cytometry appear to be valuable indicators in the evaluation of patients with prostatic carcinoma.

Follow-up on flow cytometric DNA analysis of squamous cell carcinoma of the tongue

Preliminary data from this institution suggested that flow cytometric DNA analysis was an objective prognostic indicator in archival localized squamous cell carcinoma of the tongue. Technical improvements were made, including analysis of tumor, normal tissue, and a combination of the two; standardized cursor placement; mathematic determination of tetraploid populations; and development of a statistical analysis. A larger number of patients (60) with this disease were reviewed. DNA content was related to disease-free survival, local recurrence, regional metastasis, and incidence of second primary tumors. There was no significant difference between aneuploid and diploid tumors with respect to the variables analyzed. We believe these technical improvements will enhance flow cytometric DNA analysis of paraffin-embedded tissues. However, in this retrospective review of localized squamous cell carcinoma of the tongue, DNA analysis was not a valuable prognostic indicator. Only prospective studies will address this issue.

Doxorubicin-cisplatin-vinblastine combination chemotherapy of advanced endometrial carcinoma: A Southwest Oncology Group study

A combination of doxorubicin (30 mg/m2 iv), cisplatin (50 mg/m2 iv), and vinblastine (5 mg/m2 iv) repeated every 3-4 weeks was used to treat 55 patients with advanced stage III or IV or recurrent disease. Of the 42 fully evaluable patients, there were 3 complete responders (7%) and 10 partial responders (24%). Responses were of short duration (median of 8 months, range 3-15 months) and the median survival of all evaluable patients was only 10 months from the start of therapy. Leukopenia was the major toxicity and was at least moderate in two-thirds of patients. We conclude that the addition of cisplatin and vinblastine to doxorubicin does not improve the clinical utility of doxorubicin in patients with advanced endometrial cancer.

Automated screening for quality control using PAPNET: A study of 638 negative Pap smears

To determine if the PAPNET screening system can be used for quality control to lower false‐negative rates for Pap smears 638 manually screened. “negative” Pap smears were subjected retrospectively to the PAPNET screening system. Twenty‐nine of the smears came from 18 patients who subsequently had biopsy‐proven high‐grade squamous intraepithelial lesions (SIL). The remaining 609 negative smears were arbitrarily selected as controls.

Randomized phase III trial of chemoimmunotherapy in patients with previously untreated stages III and IV suboptimal disease ovarian cancer: A Southwest Oncology Group study☆

Abstract Between 1979 and 1984, 98 patients considered to have stage III epithelial type ovarian cancer and optimal surgical resections (i.e.,

Chemotherapy of drug-resistant ovarian cancer: a Southwest Oncology Group Study.

We present a final analysis, including pathology review, of a cooperative group study of drug-resistant ovarian cancer. Of 200 patients registered, 112 were eligible and evaluable, with a response rate of 26% and median survival of 7 months. Because these results are poorer than those reported in the preliminary and interim analyses of this study, we scrutinized the 88 excluded patients, most of whom failed to meet our strict pathologic criteria for a diagnosis of ovarian cancer of epithelial type, and who, as a heterogeneous group, fared better than patients who did meet the eligibility criteria. We believe this analysis provides insight into the spectrum of diseases that are frequently called ovarian cancer, but might be more properly labeled abdominal carcinomatosis.

Phase II trial of vinblastine in previously treated patients with ovarian cancer: A southwest oncology group study

Sixty-eight patients with relapsing, epithelial type ovarian carcinoma were entered into a Phase II study of vinblastine. Vinblastine was administered as a continuous intravenous infusion over 5 days at a starting dose of 1.7 mg/m2/day every 3 weeks. There were 44 fully evaluable and 6 partially evaluable patients. Forty-one of these patients had had only one prior treatment regimen. Grade 3 or 4 leukopenia occurred in 12 patients (24%), but Grade 3 or 4 thrombocytopenia occurred in only 2 patients. There were two clinical complete responses of 18- and 36-week durations and one partial response of 6 weeks for an overall response rate of 7%. We conclude that vinblastine, administered in optimal dose and schedule, has little clinical activity in previously treated patients with ovarian cancer.

Phase II trial of amonafide in previously treated patients with advanced ovarian cancer: A Southwest Oncology Group study

Twenty-three patients with metastatic or recurrent Stage III or IV epithelial ovarian cancer who were refractory to or relapsed following previous chemotherapy with cisplatin or a cisplatin analog were entered into a phase II study of amonafide. The starting dose of amonafide was 300 mg/m2 delivered daily over 1 hr by intravenous infusion. In the absence of myelosuppression, the dose of amonafide was escalated by increments of 75 mg/m2 to a maximum of 450 mg/m2. There were 19 eligible and 17 fully evaluable patients. Grade 3 or 4 leukopenia occurred in 14 (74%) patients and grade 3 or 4 thrombocytopenia in 6 (32%) patients. No objective complete or partial responses were observed. Four patients had stable disease for 3, 4, 4.5, and 6 months, respectively. Therefore, amonafide in the doses used in the present trial does not have significant activity in previously treated patients with ovarian cancer.