William A. Nahhas

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.

Randomized placebo-controlled multicenter evaluation of diethyldithiocarbamate for chemoprotection against cisplatin-induced toxicities.

PURPOSE Diethyldithiocarbamate (DDTC) blocks cisplatin-induced toxicities in animal models without inhibiting antitumor effects. DDTC chemoprotection was tested in a randomized, multicenter, double-blind comparison versus placebo (PB) in patients with lung or ovarian cancer. Primary end points were nephrotoxicity, ototoxicity, neuropathy, and completion of therapy. PATIENTS AND METHODS Between April 1990 and February 1992, 221 patients were registered with small-cell lung cancer (SCLC), non-small-cell lung cancer (NSCLC), or ovarian cancer. Cisplatin (100 mg/m2) and cyclophosphamide (in ovarian cancer) or etoposide (in lung cancer) were administered with either DDTC (1.6 g/m2 over 4 hours) or PB intravenously, every 4 weeks for a planned six cycles. RESULTS At an interim safety analysis, data were available for 195 patients from the combined lung and ovarian cancer populations (PB, 99 patients; DDTC, 96 patients). Withdrawal for chemotherapy-induced toxicities occurred in 9% of PB-treated patients and 23% of DDTC-treated patients (P = .008). The mean cisplatin delivered dose-intensity (DDI) was 23 mg/m2/wk on both arms. However, the mean cisplatin cumulative dose delivered (CDD) was 379 mg/m2 on the PB arm, compared with 247 mg/m2 on the DDTC arm (P = .0001). At the time of interim analysis, 28% of PB-treated patients had completed all six cycles of therapy, compared with only 6% of DDTC-treated patients (P < .001). Although, clinical hearing loss, neuropathy, emesis, and myelosuppression were equivalent in the two treatment arms, DDTC-treated patients had more nephrotoxicity as determined by changes in serum creatinine concentration. Toxicities related to DDTC infusion included transient hypertension, flushing, and hyperglycemia. DDTC did not compromise response rates in either tumor type. CONCLUSION This study did not demonstrate a significant chemoprotective effect against cisplatin-induced toxicities with the DDTC dose schedule tested. Patients who received DDTC received lower cumulative doses of cisplatin, but were more likely to be withdrawn from treatment early due to chemotherapy-related toxicities.

A prospective randomized trial of thalidomide with topotecan compared with topotecan alone in women with recurrent epithelial ovarian carcinoma

Thalidomide is an antiangiogenic agent with immune modulating potential. The objective of this study was to determine response rates among women who were treated for recurrent ovarian cancer using topotecan with or without thalidomide.

Evaluation of urinary cytology of male sexual partners of women with cervical intraepithelial neoplasia and human papilloma virus infection

Condylomas of the genital tract can be found in 70% of patients who have cytologic evidence of human papilloma virus (HPV) infection or mild epithelial dysplasia (CIN I). Most male sexual partners of women with overt or subclinical HPV infections have no visible condylomas. Presently, there is no therapy for subclinically infected male partners. A screening test capable of detecting such HPV infections in males would be of value should effective therapy be discovered. Fifty-four men who were the current sexual partners of women with visible condylomata acuminata or with cytologic evidence of subclinical HPV infection or cervical neoplasia were asked to give a urine specimen for cytologic examination. The cytologist had no knowledge of the cytologic or histopathologic findings in the female partners. Of the 54 women, 39 (72%) had either visible genital condylomas or cytologic evidence of mild dysplasia or of HPV infection with or without mild dysplasia (CIN I). Twenty-five (63%) had histologic evidence of HPV infection with or without mild dysplasia. With one exception, urinary cytologic preparations from the study and from the control males were negative. No correlation could be found between cervical cytology and histology in the females and urinary cytologic findings in their current male partners. At the present time there is no screening test that can be utilized to detect male carriers with subclinical disease.

The prognostic implications of low serum CA 125 levels prior to the second-look operation for stage III and IV epithelial ovarian cancer

Second-look laparotomy is performed to evaluate response to chemotherapy and to determine the need for additional treatment. The relationship between absolute levels of serum CA 125 less than 35 u/ml and disease status at second-look operation was evaluated in 95 patients with advanced-stage epithelial ovarian cancer. Eighty-six patients had Stage III disease and nine patients had Stage IV cancer. Residual tumor was documented at second-look laparotomy in 52 (55%) of the patients studied. Forty-nine percent of the 82 patients with serum CA 125 values less than 20 u/ml had residual disease. In contrast, 12 of 13 (92%) patients with serum CA 125 values of 20-35 u/ml had residual tumor at second-look laparotomy. All patients with serous cystadenocarcinomas and serum CA 125 values of 20-35 u/ml had residual tumor, and two-thirds of these cases had grossly visible disease. The positive predictive value of a serum CA 125 level of 20-35 u/ml was 0.92. These data suggest that second-look laparotomy should be deferred in patients with advanced-stage ovarian cancer until serum CA 125 values are less than 20 u/ml.

Palliative pelvic exenteration—Futility revisited

In a retrospective review of 23 pelvic exenterations performed at Miami Valley Hospital, 8 were considered to be palliative procedures because of pelvic or paraaortic lymph node metastases, pelvic peritoneal involvement, pelvic sidewall extension, or distant spread. Following palliative exenteration, morbidity and mortality were high, survival was low, and quality of life was uniformly poor. With rare exceptions, pelvic exenteration as a palliative procedure should not be deliberately performed.

A potential hazard of the use of the surgical ultrasonic aspirator in tumor reductive surgery

The surgical ultrasonic aspirator (USA) is a recently developed surgical instrument being used for an increasingly wide range of surgical procedures including tumor reductive surgery in patients with advanced ovarian carcinoma. This paper introduces a potential hazard of the use of this instrument. It was determined that the mist produced by the ultrasonic aspirator during tumor reductive surgery contains intact and possibly viable cancer cells.

Debridement of vaginal radiation ulcers using the surgical ultrasonic aspirator

The surgical Ultrasonic Aspirator (USA) is a fairly new surgical instrument used for an increasingly wide range of procedures. This paper introduces a new application: debridement of vulvovaginal necrotic ulcers resulting from intracavitary radiation therapy. The ultrasonic aspirator allowed removal of the soft, necrotic tissue while preserving underlying healthy, firm tissue and blood vessels.

Prognostic factors and the significance of cytologic grading in invasive squamous cell carcinoma of the vulva: A clinicopathologic study

Clinical staging, tumor size, histologic differentiation, cytologic grading, depth of stromal invasion, and vascular channel involvement by tumor cells were studied in 42 patients with invasive squamous cell carcinoma of the vulva who were treated with radical vulvectomy and inguinal-femoral lymphadenectomy. All parameters were found to correlate well in predicting groin node metastasis. Cytological grading was found to be more significant compared to histologic grading in regard to nodal metastasis (P less than 0.02). No patient with cytologic or histologic grade 1 tumor and less than 5 mm stromal invasion was found to have nodal metastasis.

Significance of lymphoplasmocytic infiltration around tumor cell in the prediction of regional lymph node metastases in patients with invasive squamous cell carcinoma of the vulva: A clinicopathologic study

Abstract Histologic material from 42 patients treated for invasive squamous cell carcinoma of the vulva was studied to determine the prognostic significance of lymphoplasmocytic infiltration around tumor cells in the prediction of regional lymph node metastases. No correlation was found between lymphoplasmocytic infiltration and nodal metastasis with respect to degree of tumor differentiaton, stage of disease, and vascular channel involvement. The presence or absence of lymphoplasmocytic infiltration around tumor cells appears to have no prognostic value in predicting nodal metastases.