Prognostic impact of body mass index and effect of overweight and obesity on surgical and adjuvant treatment in early-stage epithelial ovarian cancer.

The present study was performed to find out if the body mass index (BMI) was associated with clinical and pathologic features (age, histology, tumor grade, and substages) and prognosis in early stages (FIGO I-II) of epithelial ovarian cancer. Further aims of the study were to evaluate if overweight or obesity affected the feasibility of optimal surgery and postoperative adjuvant therapy. A total of 635 patients were included in this study. Four percent of the patients were underweight (BMI <18.5), 53% were of ideal body weight (BMI 18.5-25), 31% were overweight (BMI 25-30), and 12% were obese (BMI >30). Overweight and obese patients were significantly (P = 0.006) older than underweight and ideal body weight patients. Tumor grade and histologic type distributions were not different across the BMI strata. FIGO stage (P = 0.011) and presence of ascites (P = 0.007) at primary surgery were associated with the BMI status. A history of cardiovascular disease was significantly (P = 0.006) more common in overweight and obese patients. Survival analyses in the four BMI subgroups did not show any significant differences with regard to recurrence-free survival. The 5-year recurrence-free survival of the complete series was 72%. Overweight and obese patients did not have worse survival than normal weight and underweight patients. Perioperative or postoperative morbidity and adjuvant oncologic treatment were not affected by the BMI. In a multivariate Cox analysis, FIGO substage and tumor grade, but not BMI, were independent and significant prognostic factors with regard to all types of survival rates.

Treatment of primary advanced and recurrent endometrial carcinoma with a combination of carboplatin and paclitaxel-long-term follow-up.

There is no generally accepted standard chemotherapy in treatment of advanced and recurrent endometrial carcinoma. Cisplatin and doxorubicin with or without cyclophosphamide are widely used. Response rates have improved with combination chemotherapy compared with single-agent therapy. A platinum analog seems to be an important part of the chemotherapy regimen. Since few patients are cured from their disease and since the duration of response is short, further improvement of this therapy is warranted. During the past years, the taxanes (paclitaxel) are being added to prior evaluated regimens and not only improved response rates are reported but also increased toxicity is observed. In a prospective, phase II, multicenter study, carboplatin (area under the curve = 5) and paclitaxel (175 mg/m(2)) were evaluated in treatment of primary advanced and recurrent endometrial carcinoma. In total, 66 patients were recruited during the years 2000-2004. Eighteen primary advanced tumors and 48 recurrences were treated. All histologic types and tumor grades were allowed. The median follow-up was 57 months (range 37-69 months). The overall response rate was 67% (95% CI 55-78). The complete response rate was 29% and the partial response rate 38%. Primary advanced and recurrent tumors as well as endometrioid and nonendometrioid tumors showed similar response rates. The median response duration was 14 months. The 1- and 3-year survival rates were 82% and 33%, respectively. The main toxicities were hematologic and neurologic (sensory neuropathy). The response rates were encouraging, superior to prior platinum-containing regimens, but response duration and the long-term survival rate were still short. The neurologic toxicity was frequent and was a substantial problem in this series of patients. Further research is highly needed to improve the treatment of advanced and recurrent endometrial cancer.

Randomized trial of recombinant human interleukin-3 versus placebo in prevention of bone marrow depression during first-line chemotherapy for ovarian carcinoma.

PURPOSE: To determine whether recombinant human interleukin-3 (rhIL-3) reduces bone marrow depression and improves chemotherapeutic schedule adherence in ovarian cancer patients receiving first-line combination chemotherapy. PATIENTS AND METHODS: In a randomized multicenter study, 185 patients received carboplatin (dose based on projected area under the concentration-time curve [AUC]=4) and cyclophosphamide (750 mg/m2) day 1, every 3 weeks for six cycles. Patients were randomized to receive rhIL-3 (5 microg/kg) or placebo once daily subcutaneously on days 3 to 12. RESULTS: Adherence to chemotherapeutic regimen, mean chemotherapy cycle length, tumor response rate, and median survival at 24 months did not differ between groups. The number of side effects-primarily allergic reactions, flu-like symptoms and fever-were higher in the rhIL-3 group, which resulted in 21 discontinuations compared with one in the placebo group. Compared with placebo, the rhIL-3 group had higher platelet counts day 1 of cycles 2 to 6. The number of patients with World Health Organization (WHO) grade IV thrombocytopenia or number of platelet transfusions did not differ. Leukocyte counts differed only in cycles 1 and 2 between groups. The leukocyte nadir occurred earlier in the rhIL-3 (day 12) than in the placebo group (day 15, P=.006). Leukocytes and neutrophils were only higher in the rhIL-3 group day 1 of cycle 2. In cycles 4 and 5, more patients with WHO grade IV neutropenia received rhIL-3 (P < .005). Eosinophil counts were higher day 1 of cycles 2 to 6 in the rhIL-3 group (P < .0001). CONCLUSION: rhIL-3 had stimulatory hematopoietic effects. This did not result either in reduction of platelet transfusions or in improvement of chemotherapeutic schedule adherence. There were more side effects in the rhIL-3 group than in the placebo group. rhIL-3 at 5 microg/kg/d is, therefore, not of clinical benefit in this chemotherapeutic regimen.

Lymph node sampling is of prognostic value in early stage epithelial ovarian carcinoma.

PURPOSE: The importance of lymph node involvement as a prognostic factor is still under debate. In the present study, the impact of surgical staging for prognosis in early stages of epithelial ovarian cancer was evaluated in a series of 113 patients. MATERIAL AND METHODS: A retrospective study was carried out at the Department of Gynecological Oncology, Orebro University Hospital, during the period 1994-1998. In a subgroup of 20 out of 113 patients, pelvic lymph node sampling or pelvic lymphadenectomy was included in the standard surgical procedure. In cases of positive lymph nodes, the tumors were upstaged to FIGO Stage III. Pearson's chi-square, the t-test, the log-rank test and Cox multivariate analysis were used in the statistical analyses. RESULTS: The 20 patients with lymph node sampling or lymphadenectomy were compared with the remaining 93 patients without a comprehensive surgical staging procedure. A survival analysis demonstrated a significant (p = 0.005) difference in disease-free survival rates between the two subgroups, where there was a survival benefit in the subgroup of patients who had undergone comprehensive surgical staging. In a Cox proportional hazard regression analysis with disease-free survival as the endpoint, high tumor grade (HR = 3.14) and comprehensive surgical staging with at least a node sampling (HR = 0.09) were significant and independent prognostic factors. CONCLUSION: The benefit in survival after the procedure of lymph node sampling in early stages of epithelial ovarian carcinoma could probably be explained by the fact that the surgical procedure detects otherwise unrecognized Stage III disease.

Efficacy and tolerability of tropisetron in comparison with a combination of tropisetron and dexamethasone in the control of nausea and vomiting induced by cisplatin-containing chemotherapy.

In a double-blind, randomised, multicentre study, the efficacy and tolerability of tropisetron and a combination of tropisetron and dexamethasone were compared for the control of nausea and vomiting induced by cisplatin in patients previously not entirely protected by tropisetron monotherapy. In all, 160 women with gynaecological cancers were studied during two consecutive courses of cisplatin-containing chemotherapy. During the first course (the screening course), all patients received tropisetron monotherapy [5 mg intravenous (i.v.) on day 1 and 5 mg orally on days 2-6] as antiemetic treatment. During the second course (the test course), tropisetron was compared with a combination of tropisetron and dexamethasone (20 mg i.v. on day 1 and 4.5 mg twice daily on days 2-6). This part of the study was double-blind, randomised and placebo-controlled. Candidates for randomisation were patients with partial control of nausea (< 12 h of nausea) or partial control of vomiting (1-4 episodes of vomiting) during the screening course. Patients with complete control of nausea and vomiting in the screening course continued with tropisetron monotherapy; patients with treatment failure received open rescue treatment in course 2. Total control of acute nausea was achieved in 37% of the tropisetron + placebo group and in 75% of the tropisetron + dexamethasone group (P = 0.001). Significantly more patients on tropisetron-dexamethasone than on tropisetron-placebo were also free of delayed nausea. Acute vomiting was prevented in 40% of the patients in the placebo group and in 75% in the dexamethasone group (P = 0.001). Delayed vomiting was also significantly less frequent in dexamethasone-treated patients than in placebo-treated patients. Tropisetron was well tolerated both as monotherapy and in combination with dexamethasone. The most frequent adverse events were headache (34%), constipation (12.5%) and fatigue (12.5%). Adding high doses of a corticosteroid did not induce further adverse events or disregulate concurrent diseases.

Tropisetron (Navoban) alone and in combination with dexamethasone in the prevention of chemotherapy-induced emesis: the Nordic experience.

Three Nordic multicenter studies were performed between 1988 and 1992 to evaluate the efficacy of tropisetron (Navoban; Sandoz Pharma Ltd, Basel, Switzerland) as an antiemetic agent in patients undergoing various types of chemotherapy. More than 1,050 patients were recruited from cancer centers in Sweden, Finland, and Denmark. In the first two studies, chemotherapy-naive patients were studied for 6-day periods over two consecutive treatment cycles. The first study comparing tropisetron with a metoclopramide cocktail was performed as an open, randomized, multicenter, parallel-group study. All 259 chemotherapy-naive patients received cisplatin > or = 50 mg/m2 on the first day of chemotherapy; other cytostatic agents were allowed on days 1 to 6 of therapy. Patients received either tropisetron or an antiemetic cocktail of metoclopramide, dexamethasone, and lorazepam over the study period. Total control of acute vomiting during the first course of chemotherapy was achieved in 63% of patients in the tropisetron treatment group and in 64% of patients in the antiemetic cocktail group. Acute nausea was prevented completely in 40% of patients in the tropisetron group and in 61% of the metoclopramide cocktail group during course 1 (P < .001). For delayed nausea and vomiting, there were no significant differences between the two antiemetic regimens. Both antiemetic regimens were well tolerated. The second study compared the efficacy of tropisetron plus placebo with tropisetron plus dexamethasone for the prevention of acute and delayed nausea and vomiting during cisplatin-containing chemotherapy in patients not fully controlled by tropisetron monotherapy during course 1. One hundred sixty patients were involved in this double-blind, randomized, placebo-controlled trial. Acute vomiting was completely prevented in 40% of patients treated with tropisetron plus placebo compared with 75% of patients treated with tropisetron plus dexamethasone (P = .001). The results for acute nausea were similar. Delayed vomiting and delayed nausea were completely prevented in significantly more patients receiving the tropisetron-dexamethasone combination than in those receiving the tropisetron-placebo combination (P < .05). Adverse events were reported less frequently in patients receiving tropisetron together with dexamethasone. The third study was an open, nonrandomized multicenter trial designed to investigate the long-term antiemetic effect of tropisetron on various types of chemotherapy and on various types of patients. An interim analysis of this study has been reported previously (Ann Oncol 4:539-542, 1993). Six hundred thirty patients were studied over a mean number of 4.6 courses (range, 1 to 19 courses) of chemotherapy. Each received tropisetron daily on days 1 to 6 of therapy. Complete protection from nausea and vomiting was achieved in 67% of the complete series. The long-term effects of tropisetron therapy remained consistent over 10 consecutive courses of chemotherapy. Tropisetron was more effective during noncisplatin treatment compared with cisplatin treatment; it was also more effective in men and in older patients (> 50 years of age). The most frequent adverse events were headache (18%) and constipation (8%).

Postoperative vaginal irradiation with high dose rate afterloading technique in endometrial carcinoma stage I.

A high dose rate (60Co) afterloading technique was used for postoperative prophylactic vaginal irradiation in a series of 404 women with endometrial carcinoma Stage I. The total recurrence rate was 3.7% with 0.7% vaginal deposits. The crude 5-year survival rate for the complete series was 91.8% compared to 13.3% for those with recurrences. Depth of myometrial infiltration (greater than 1/3 of the uterine wall) and nuclear grade were the most important prognostic factors. Clinically significant late radiation reactions (bladder and/or rectum) were recorded in 6.9%. Dose per fraction and the size of the target volume were highly significantly related to the occurrence of both early and late radiation reactions. Vaginal shortening is closely related to the dose per fraction, length of the reference isodose, and the applicator diameter. The shape of the vaginal applicator versus the isodoses and the importance of the source train geometry and relative activity for dose gradient inhomogeneities within the target volume are discussed. Cumulative radiation effect (CRE) and linear-quadratic (LQ) calculations have been performed and related to tissue reactions within the target volume and in the risk organs. An alpha-beta quotient of 8.8 for vaginal shrinkage effect and 2.0 for late rectal complications are suggested on the basis of calculations using a maximum likelihood method for quantal radiation data.

Tropisetron, a new 5-HT3-receptor antagonist, in the prevention of radiation-induced nausea, vomiting and diarrhoea.

Oral tropisetron, a 5-hydroxytryptamine type 3 (serotonin3) [5-HT3]-receptor antagonist, at a dose of 5mg daily was evaluated as antiemetic prophylaxis during postoperative abdominal irradiation. 20 women with International Federation of Gynecology and Obstetrics (FIGO) stage I to III ovarian carcinoma were included. 12 women received irradiation of whole abdominal fields and 8 of lower abdominal/pelvic fields. Efficacy and adverse events were recorded by the patients in diary-form booklets. The cumulative weekly incidence of patients with nausea, which was generally mild and of short duration, increased from 30% at the start of radiotherapy to 54% at the end of treatment. Episodes of vomiting occurred in less than 10% of the patients. Diarrhoea was common towards the end of the radiotherapy courses, and the proportion of patients needing extra antidiarrhoeal medication (loperamide) increased from 38% during the first week to 100% at the end of the radiotherapy course. Mean weight loss was 1.2kg during the 5- to 6-week course. Overall ratings for quality of life were excellent or good in 75 to 85% of patients. Tropisetron seems to be a promising and well tolerated drug in conjunction with extended radiotherapy of abdominal fields. This was an open study, establishing the methodology for long term follow-up of patients during fractionated radiotherapy.

Tropisetron, a new 5-HT3 receptor antagonist, in the prevention of radiation-induced emesis.

Tropisetron, a 5-HT3 receptor antagonist, was evaluated as antiemetic prophylaxis during postoperative abdominal irradiation of ovarian carcinoma patients. Twenty consecutive women with stages I-III (FIGO) epithelial ovarian carcinomas were included. Nausea, generally mild and of short duration, increased from start (30%) to end of radiotherapy (54%). Episodes of vomiting were few in number and occurred in less than 10% of the cases. Diarrhea was common toward the end of the radiotherapy courses. The overall ratings for quality of life were excellent or good in 75-85% of the cases. Tropisetron seems to be a promising and well-tolerated drug in conjunction with extended radiotherapy.

Betamethasone-dixyrazine combination versus high-dose metoclopramide as antiemetic treatment in doxorubicin and cisplatin chemotherapy.

In a prospective randomized and double-blind cross-over study, a new antiemetic regimen consisting of betamethasone (1 x 8 mg) and dixyrazine (a phenothiazine derivative) (4 x 10 mg) was compared with a standard high-dose metoclopramide (4 x 1 mg/kg) schedule for antiemetic treatment in doxorubicin and cisplatin chemotherapy. 100 consecutive patients (62 without prior experience of chemotherapy and 38 with prior experience) entered the study and were followed during 1-4 courses of chemotherapy. Effect and side effect parameters were recorded on questionnaires for patients and nurses using the visual analog scale for quantification. The correlation between the two ways of recording (self-scoring versus recording by nursing staff) was very high, both for effect variables (nausea and vomiting) and the adverse reactions (sedation and extrapyramidal reactions). The median number of courses per patient was 3.0 (range 1-4) and altogether 299 courses were studied. Full emetic protection was achieved in 58% with betamethasone-dixyrazine and in 34% with high-dose metoclopramide regardless of prior patient experience or the cytostatic agents administered. With doxorubicin regimens, betamethasone-dixyrazine gave full protection in 80% compared to 40% for metoclopramide. Cisplatin regimens were a greater challenge and protection against nausea and vomiting was achieved only in 27% with betamethasone-dixyrazine and in 18% with metoclopramide. Adverse reactions were a significant problem with metoclopramide: restlessness 33%, akathisia 19%, parkinsonism 16%, and acute dystonia 3%. Sedation was the same with the two regimens (80%).

Adjuvant radiotherapy in early stage ovarian carcinoma.

In a series of 228 women diagnosed with malignant ovarian tumors during the years 1980-87 radiotherapy was added as postoperative adjuvant therapy. Twenty-three cases with epithelial borderline carcinomas and 18 cases with nonepithelial tumors were excluded from the analysis. The remaining 187 cases of invasive epithelial ovarian carcinoma in FIGO stage I-II was a complete, consecutive, and total geographic series. After primary staging surgery lower abdomino-pelvic or whole abdominal radiotherapy was administered. The dose to the upper part of the abdomen was 20 Gy (fraction dose 1.0 Gy) and to the lower part and the pelvis 40 Gy (fraction dose 1.7 Gy). The patients were followed up for at least 10 years. During the follow-up 75 tumors (40%) recurred and were then treated with cisplatin-containing chemotherapy. Abdomino-pelvic (18%) and abdomino-pelvic-distant metastases (11%) were most frequent. Mean time to recurrence was 26 months. The 5-year overall survival of the complete series was 57% and the cancer-specific survival 66%. FIGO stage and tumor grade were the only independent and significant prognostic factors in a Cox multivariate analysis. Only cases in FIGO stage IA and grade 1 could be classified as low-risk cases with 5-year survival of 87%. All other cases showed a significantly worse prognosis and should be classified as intermediate or high-risk cases. Early radiation reactions were frequent (80%) but of little clinical significance. In 21 cases (11%) late radiation reactions were recorded. In 8 cases (4%) the reactions were regarded as severe and required surgical intervention or disabled the patient significantly. The results compare well with others reported in the literature.

Prognostic importance of DNA ploidy and p53 in early stages of epithelial ovarian carcinoma.

Patients with early stages (FIGO stages IA-IIC) of ovarian cancer continue to experience tumor relapses and they succumb due to their disease after seemingly adequate adjuvant therapy. In a series of 113 patients treated with adjuvant radiotherapy 4-6 weeks after primary surgery, the DNA content and p53 status of the tumors were studied and related to other known prognostic factors (age, FIGO stage, histopathologic type, and tumor grade). The DNA analyses were done by flow cytometry and p53 expression was studied by immunohistochemistry on formalin-fixed and paraffin-embedded tissue. DNA analyses of 103 tumors could be made and the p53 status was determined in 106 cases. Univariate analyses showed that both p53-positivity and aneuploidy of the ovarian tumors were strongly associated with tumor grade. There was also a strong association between p53 expression of the tumors and DNA aneuploidy (DNA index >1.10 and S-phase fraction >11.5%). P53-positivity and tumor grade were the only significant factors for the risk of tumor recurrence. DNA and p53 status alone were not adequate predictive factors to identify clinically relevant subgroups of patients who would benefit from adjuvant postoperative therapy. Tumor grade remains the most important prognostic factor with regard to the risk of tumor recurrence and the cancer-specific survival rate in early stage ovarian carcinoma. Overexpression of p53 also increases the risk of tumor recurrence.

Treatment of cervical-carcinoma by wertheim-meigs surgery - long-term follow-up results in a well-defined Swedish region.

In a retrospective analysis of a complete geographic series of cervical carcinomas treated by Wertheim-Meigs radical surgery, a number of important prognostic factors were evaluated and long-term survival data are presented. In all, 367 women with FIGO stage I-II tumors were included. The main histopathologic types were squamous cell carcinoma in 84% and adenocarcinoma in 12%. The mean age of the patients was 42.5 (range 19-68) years. In 125 women (34%), adjuvant radiotherapy was administered pre- or postoperatively. The median period of follow-up was 12 (range 2-27) years. In 88% of the specimens surgery (93% in stage I and 66% in stage II) was classified as radical with regard to the excision margins. This was an important and highly significant prognostic factor. If the margins were wide and free of tumor, the 10-year survival rate was 93%, but if margins were infiltrated by the tumor, the survival rate was 14%. Pelvic lymph node involvement was recorded in 52 cases (14%). The frequency of lymph node spread was associated with tumor stage (IA O%, IB 14%, IIA 32%). The probability of survival of the complete series was 93% at 5 years and 84% at 10 years. In cases of lymph node involvement, the 10-year survival rate was 57%. The preoperative tumor stage had a highly significant influence on long-term tumor-specific survival. Tumor grade was also a significant prognostic factor, but not the histologic type (squamous, adenosquamous, or adenocarcinoma). Age and parity were also insignificant prognostic factors. The tumor recurred in 59 cases (16%). The mean time to relapse was 28 months. The 10-year survival was 29% for this group of patients. Peroperative complications were recorded in 50 patients (14%). Excessive bleeding (11%) and urinary tract injuries (3%) were most frequent. Postoperatively, 101 patients (28%) had some kind of complication associated with the surgical procedure. Surgical complications were more frequent among women over 50 years of age. Bladder dysfunction (11%) and obstruction of the ureter (8%) were recorded most frequently. In 19 cases (5.2%), urinary tract or intestinal fistulas were diagnosed during the period of follow-up. With increasing experience of the surgeons and fewer stage II tumors, the frequency of fistulas associated with the surgical procedure decreased to 2.4% during the latter part (1975-90) of the period. Adjunctive postoperative radiotherapy increased the risk of late complications. In 8 cases (6.4%), serious complications associated with the combination of surgery and radiotherapy were reported.

Active pharmacologic management of the third stage of labor. A comparison of oxytocin and ergometrine.

Postpartum hemorrhage is a common and serious complication of the third stage of labor resulting in anemia and increased morbidity in the puerperium. Administration of uterotonic drugs and suitable mechanical assistance in delivery of the placenta may significantly reduce this hazard. Ergometrine and oxytocin have been used for a long time in markedly different doses and by various routes of administration with varying success. In order to compare these two oxytocics with regard to their hemostatic effects as well as their possible interference with the physiologic placental separation mechanism, three groups (ergometrine, oxytocin, and control) of women have been studied during a 2-year period. Ergometrine (0.2 mg) and oxytocin (10 IU) administered in the stated doses and as single intravenous injections are comparable with regard to hemostatic efficiency, but oxytocin seems to promote placental separation and expulsion better and thereby reduces the risk of partial retention and trapping with bleeding reguiring further emergency measures as a frequent consequence.

Bleomycin-adriamycin-cisplatin combination chemotherapy in the treatment of primary advanced and recurrent cervical carcinoma.

A chemotherapeutic combination of bleomycin-adriamycin-cisplatin has been used to treat 21 consecutive patients with primary advanced or recurrent cervical carcinomas. Four complete (19.0%) and four partial remissions were recorded. The responding patients had significantly longer survival levels compared with the remaining 13 with stable disease. No patient had progressive disease during treatment. The median survival of the complete series was 9.2 months. The objective response rate was 14.3% for tumors within previously irradiated pelvic tissues but 100% (75.0% complete remissions) for distant metastases. Anemia, anorexia, and progressive weakness were troublesome side effects, however, and they seriously limited the clinical usefulness of this bleomycin-adriamycin-cisplatin regimen in the treatment of primary advanced and recurrent cervical carcinomas.

Importance of histologic grading in the prognosis of epithelial ovarian carcinoma.

Ovarian epithelial carcinomas still have a poor prognosis. Great efforts are being made to improve treatment modalities; chemotherapy in particular is in a period of dynamic development. A basic requirement for the necessary research is a thorough knowledge of the natural history of ovarian cancer and its prognostic influence. In this report the importance of tumor stage, histologic type, and degree of differentiation is analyzed in an unselected and well-controlled Swedish ovarian cancer series comprising 501 cases. The great prognostic significance of tumor grade for survival is demonstrated and it is proposed that this histopathologic factor, as well as tumor stage and histologic type, should be included in the international classification of primary epithelial tumors of the ovary.

VM-26-vincristine-cisplatin combination chemotherapy in the treatment of primary advanced and recurrent endometrial carcinoma.

A chemotherapeutic combination consisting of VM-26-vincristine-cisplatin was used to treat 44 consecutive patients with primary advanced or recurrent endometrial carcinomas. Nine complete remissions (20.5%) and 14 partial remissions (31.8%) were recorded. The median duration of remission in responders was 8 months (range 1-35). The responding patients had significantly longer survival than nonresponders. The median duration of survival in the complete series was 7 months. The response rates and survival times were the same for primary advanced tumors and recurrences, regardless of sites. Peripheral neuropathy, secondary anemia, and nausea were the most common side effects. The drug combination was well tolerated, and its efficacy is comparable to that of other more toxic chemotherapy regimens.

An open, randomized study to compare the efficacy and tolerability of tropisetron with that of a metoclopramide-containing antiemetic cocktail in the prevention of cisplatin-induced emesis.

In a prospective randomized study comprising 66 women treated for gynecologic malignancies with cisplatin-containing chemotherapy, the new 5-hydroxytryptamine3 (5-HT3) receptor antagonist tropisetron (Navoban, Sandoz Pharma Ltd.) was compared with a metoclopramide cocktail for the prevention of nausea and emesis. All patients were chemotherapy-naive. Two consecutive courses (including the 1st week posttherapy) were studied. The cisplatin doses were in the range of 50-75 mg/m2, and the regimens also contained doxorubicin, teniposide, etoposide, vincristine, and bleomycin. Complete protection against nausea during the first 24 h (course 1) was achieved in 76% of the tropisetron group and in 85% of the metoclopramide group. Emesis was prevented in 82% of the patients in both groups. During the whole 6-day period, full emetic protection was achieved in 30% and 18% of the patients in the two groups. On days 3-4 of course 1, tropisetron was superior to metoclopramide. The overall tolerability of the tropisetron was excellent or good in 94% of patients, a rate higher than that observed for the metoclopramide regimen (75%). The most common side effects for the latter regimen were sedation (82%) and extrapyramidal reactions (21%). The only significant adverse event recorded after treatment with tropisetron was headache of slight or moderate grade.

Relation between HPV-DNA and expression of p53, bcl-2, p21WAF-1, MIB-1, HER-2/neu and DNA ploidy in early cervical carcinoma: correlation with clinical outcome.

The purpose of the present study was to analyze the relation between the expression of p53, bcl-2, p21WAF1, MIB-1, HER-2/neu, DNA ploidy and HPV16 or 18 infections with clinical parameters. HPV-DNA was evaluated in 171 early cervical carcinomas treated from 1965 to 1990 and detected by PCR (polymerase chain reaction) on paraffin specimens obtained before therapy was started. HPV-DNA of any type was detected in 78% (86/110) of all tumors, HPV16 was the predominant type and was seen in 56% (62/110), HPV18 in 8% (9/110) and HPV35 in 21% (23/110). Patients with HPV16 or 18 were significantly (P=0.011) younger than patients with tumors not containing these two HPV subtypes. Lymph node metastases were seen more frequently (P=0.047) in tumors expressing HPV16 or 18. Tumor size was associated with the HPV-type. The frequency of DNA aneuploidy was lower in high-risk HPV tumors than in tumors with other HPV subtypes (P=0.014). MIB-1 expression was highly significantly (P=0.00007) associated with presence of HPV16 or 18. The cancer-specific survival rate was lower for patients with HPV16 and 18 positive tumors, but the difference was not statistically significant. The overall 5-year survival rate of the complete series was 91%. In conclusion, the HPV DNA subtype was a prognostic factor in early stage cervical cancer and it was associated with age, positive lymph nodes, tumor size, DNA ploidy and the proliferation marker MIB-1.

Polyclonal cervical tumors detected by flow cytometry.

In a prospective study, the tumors of 167 patients with invasive squamous cell carcinomas of the uterine cervix were investigated by flow cytometric measurements of the DNA-content. In 37 patients (22%) 2 or more stemlines could be detected, indicating clonal heterogeneity. The proportion of multiple stemlines was equal in stages IB to III but significantly higher in stage IV (p less than 0.01). In 14 of the 37 polyclonal tumors the DNA-value of the second peak was twice the value of the first peak, suggesting possible polyploidization. For those tumors with evidence of polyploidization that had values in the diploid, tetraploid or octaploid region (n = 9) the mean age was 35.6 +/- 11.7 years and for grossly aneuploid tumors (n = 5) the mean age was 73 +/- 12.6 years. The differences of mean age between the two groups differed significantly (p less than 0.001). Flow cytometry proved to be a useful, rapid, and sensitive method for detection of multiple stemlines.