Epoetin alfa in platinum-treated ovarian cancer patients: results of a multinational, multicentre, randomised trial.

This multicentre, open-label, controlled clinical trial assessed the effects of epoetin alfa treatment on haematologic and quality of life (QOL) parameters in 182 anaemic (Hb< or = 12 g dl(-1)) ovarian cancer patients receiving platinum chemotherapy. Patients were randomised 2 : 1 to receive epoetin alfa 10,000-20 000 IU three times weekly plus best standard treatment (BST) or BST only. Main study end points were changes from baseline in haemoglobin (Hb) level, transfusion requirements, and QOL. For the epoetin alfa group, mean Hb increased by 1.8 g dl(-1) by weeks 4-6 and was significantly increased from baseline through study end (P<0.001). The mean change in Hb from baseline was significantly (P<0.001) greater for epoetin alfa than BST patients at all post-baseline evaluations. Significantly fewer epoetin alfa than BST patients required transfusion(s) after the first 4 weeks of treatment (7.9 vs 30.5%; P<0.001). Also, significant (P< or = 0.04) differences favouring the epoetin alfa group over the BST group were found for all three median CLAS scores (Energy Level, Ability to Do Daily Activities, Overall QOL) and the median average CLAS score during chemotherapy. These findings support use of epoetin alfa to increase Hb levels, reduce transfusion use, and improve QOL in anaemic ovarian cancer patients receiving platinum chemotherapy.

Prognostic significance of preoperative DNA flow cytometry in surgically-treated cervical cancer.

OBJECTIVE: To evaluate the prognostic significance of preoperative DNA flow cytometry compared with other clinical and histologic variables in cervical carcinoma. STUDY DESIGN: Sixty-four patients with FIGO Stage Ib-II cervical cancer treated with radical abdominal hysterectomy and systematic pelvic lymphadenectomy were analyzed. The mean follow-up was 3.4 (range 0.3-9.8) years. DNA flow cytometry was performed with fresh tumor tissue. Four biopsies were recut from the surgical specimen within 30 minutes of the operation. The ectocervix was divided into four quadrants and a specimen obtained from each. DNA-low-grade tumors (diploid, near-diploid, tetraploid and near-tetraploid) were distinguished from DNA-high-grade tumors (aneuploid and hypoploid). Carcinomas with more than one non-diploid stem line were considered heterogeneous. An S phase fraction >7% was classified as low, 7% - < 14% as moderate, and > or = 14 as high. DNA ploidy, DNA heterogeneity, S phase fraction and various clinical and histological variables were related to disease-free survival. RESULTS: In the univariate analysis patients with DNA-low-grade carcinomas had significantly better disease-free survival than patients with DNA-high-grade tumors (82% vs 45%, p = 0.021). Carcinomas with an S-phase fraction < 7% were associated with better disease-free survival (0.8) than those with an S-phase fraction 7% - > 14% (0.62) and those with > or = 14% (0.64), but this was not statistically significant. Cox stepwise regression analysis showed DNA-heterogeneity, age, grade, parametrial involvement and extrapelvic metastasis to be independent prognostic factors. CONCLUSION: DNA ploidy and DNA heterogeneity are of prognostic importance in cervical cancer. DNA flow cytometry may be used preoperatively to identify low-risk and high-risk patients within a given stage.

Tumor progression, histologic grading and DNA-ploidy as predictive factors of lymphogenous metastasis in primary carcinoma of the Fallopian tube.

UNLABELLED: The bad prognosis of primary carcinoma of the Fallopian tube (FTC), with 5-year overall survival rates of only 35%, is particularly ascribed to lymphogenous metastasis. Yet, we know very little on the pathophysiologic factors on which this lymphogenous metastasis is based. The present study, therefore, aims at evaluating the influence of intra-abdominal tumor progression and tumor-cell anaplasia on lymphogenous metastasis in FTC. We studied 41 cases of FTC, who had been subjected to radical lymphadenectomy during primary operation in a retrospective analysis. Staging was done by International Federation of Gynecology and Obstetrics-classification. Histologic grading and nuclear DNA-content (DNA-index) were used for evaluating tumor-cell anaplasia. Histologic grading discriminated between highly differentiated (G1), moderately dedifferentiated (G2), and dedifferentiated (G3) tumors. According to their DNA-indices, tumors were separated into three groups: DNA-index < or =1.1 (euploid cases), DNA-indices between 1.1 and 2.0 (cases of intermediate ploidy), and DNA-index >2.0 (aneuploid cases). The overall incidence of lymph node metastases was 43.9%. There was no correlation between histologic grading and DNA-index (P=0.98). Lymphogenous metastasis set in after the tumor had transgressed the tube (intra-abdominal stage II). Further intra-abdominal tumor progression (including omentum, liver, or peritoneum) significantly increases the incidence of lymph node metastases (P=0.02). There was only a single G1-tumor that had already disseminated into the lymph, all other cases of lymph node metastases were found in G2- or G3-tumors. DNA-index and the extent of lymphogenous metastases were not found to be correlated (P=0.74). CONCLUSIONS: The extent of lymphogenous metastases in FTC depends above all on intra-abdominal tumor progression. This fact has clinical consequences as the indication for lymphadenectomy can be obtained directly during operation. The results of histologic grading are of no impact on the surgical proceedings; the determination of DNA-ploidy is negligible.

Cervical intraepithelial neoplasia III: long-term outcome after cold-knife conization with clear margins.

OBJECTIVE: To evaluate the long-term outcome of patients with severe cervical intraepithelial neoplasia or squamous cell carcinoma in situ (CIN III) after cold-knife conization with clear margins. METHODS: A total of 4417 women (mean age 36, range 18-72 years) with histologically confirmed CIN III had cold-knife conization with clear margins at our institution between 1970 and 1994. All patients were followed up with colposcopy, cytology, and pelvic examination for a mean of 18 years (range 5-30years). RESULTS: New high-grade squamous intraepithelial lesions (SILs) (CIN II and III) developed in 15 (0.35%) patients (mean age 35, range 25-65 years) after a median of 107 (range 40-201) months. A total of 4402 (99.65%) patients (mean age 36, range 18-72 years) were free of high-grade SILs after a mean follow-up of 18 (range 5-30) years. High-grade glandular intraepithelial lesions developed in two (0.05%) patients 14 and 17 years after conization. Twelve (0.3%) patients had metachronous vulvar intraepithelial neoplasia (VIN) grade III or vaginal intraepithelial neoplasia (VAIN) grade III, and one (0.02%) patient had invasive vaginal carcinoma 10 years after conization. CONCLUSION: Cold-knife conization with clear margins was an adequate method to definitively treat CIN III.

The relevance of adjuvant therapy in primary carcinoma of the fallopian tube, stages I and II: irradiation vs. chemotherapy.

INTRODUCTION: Primary carcinoma of the Fallopian tube (FTC) is a rare but extremely aggressive neoplasm. It must be expected to cause up to 40% of tumor-related deaths even in Stage I, and up to 57% in Stage II. Due to its rarity, there exist only a few and divergent reports on the value of adjuvant therapy. Therefore the present study aims at evaluating the influence of postoperative adjuvant therapy on FTC by studying the effects of irradiation and chemotherapy on the overall survival of patients in Stages I and II. PATIENTS AND METHODS: We investigated 95 cases of FTC in Stages I (n = 66) and II (n = 29) in a retrospective multicenter study. Group I (n = 32) are patients who underwent a complete irradiation with cobalt or photon energies of 23 MV (administering a daily dose of 2 Gy resulted in a total of 45-52 Gy in the pelvic areas). Group II (n = 31) consists of those cases who received postoperative chemotherapy with platinum. Thirty-two women were excluded from this study because they had other chemotherapies, incomplete irradiation, or no adjuvant therapy at all. RESULTS: Median survival time was 57 months in Group I patients (95% confidence interval 33-81 months), compared to 73 months (95% confidence interval, 68-78 months) in the chemotherapeutically treated Group II. This difference did not prove to be statistically significant (p = 0.476).If primary surgical therapy is included in the evaluation, and patients with total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO) are compared to those with additional radical lymphadenectomy (TAH+BSO+lymph nodes), the latter group's overall survival essentially improves but fails to reach statistical significance. Their 5-year survival rate is 83% against 58% in the TAH+BSO group (p = 0.12). CONCLUSION: Chemotherapy and irradiation are two adjuvant therapies that are similarly effective in FTC of Stages I and II, with chemotherapy being preferred at the present time. Primary surgical treatment, however, is of crucial impact on the prognosis of FTC.

The clinical value of serum concentrations of cancer antigen 125 in patients with primary fallopian tube carcinoma: a multicenter study.

BACKGROUND: Primary fallopian tube carcinoma (PFTC) is a rare disease, and data on the serum concentration of tumor marker cancer antigen 125 (CA 125) in patients with this disease are sparse. The authors assessed the clinical value of the serum concentration of CA 125 as a prognostic and monitoring marker in patients with surgically treated PFTC. METHODS: In a multicenter study, the concentration of CA 125 was measured in 406 serum samples from 53 patients with PFTC. The results were correlated with clinical data. RESULTS: The pretreatment median serum CA 125 level was 183 U/mL (range, 6.5-5440.0 U/mL) in patients with PFTC. In a univariate Cox regression model, tumor stage and serum CA 125 level were associated significantly with shortened disease free survival (P = 0.006 and P < 0.001, respectively) and with overall survival (P = 0.03 and P = 0. 001, respectively). Lymph node involvement, tumor grade, and patient age were not associated with the length of survival. A multivariate Cox regression model showed that pretreatment the serum CA 125 level was a prognostic factor of disease free and overall survival, independent of tumor stage (P = 0.005 and P = 0.01, respectively). The pretreatment serum CA 125 level was correlated with tumor stage (P < 0.001) but not with lymph node involvement (P = 0.8), histologic grade (P = 0.3), or patient age (P = 0.2). The serum CA 125 level during chemotherapy was correlated significantly with Gynecologic Oncology Group response criteria to chemotherapy (P = 0. 001). During the follow-up of patients, serum CA 125 levels reached sensitivity, specificity, positive predictive value, and negative predictive value of 92%, 90%, 67%, and 98%, respectively, for differentiating between no evidence of disease and the presence of recurrent disease. In 90% of the patients, an increase of serum CA 125 level preceded the clinical or radiologic diagnosis of recurrent disease with a median lead time of 3 months (range, 0.5-7.0 months). CONCLUSIONS: This is the largest study to date with respect to serum CA 125 levels in patients with PFTC. The current data indicate that the pretreatment serum CA 125 level is an additional independent prognostic factor of disease free and overall survival in patients with PFTC. The serum CA 125 level adequately defines the response to chemotherapy and displays good sensitivity and specificity characteristics during the follow-up of patients with PFTC.

Expression of oestrogen and progesterone receptors in low-grade endometrial stromal sarcomas.

We analysed oestrogen receptor (ER) and progesterone receptor (PR) expression in a retrospective series of 21 low-grade endometrial stromal sarcomas (LGSSs). Archival formalin-fixed and paraffin-embedded material was analysed by immunohistochemistry. ER and PR were measured with monoclonal antibodies and the peroxidase-antiperoxidase method and a score was calculated as for breast carcinoma based on both the percentage of positive tumour cell nuclei and the staining intensity. ER were seen in 15 (71%) and PR in 20 (95%) of tumours respectively. ER expression was scored as high in three (14%), moderate in four (19%), and low in eight (38%) tumours. Six (29%) tumours did not stain for ER and all of these were positive for PR. PR expression was scored as high in eight (38%), moderate in ten (47%) and weak in two (10%) LGSSs. Only one (5%) LGSS did not stain for PR (this tumour was positive for ER). ER and PR expression in LGSS is heterogeneous. This may have implications for hormone therapy in the management of these tumours. These results suggest that ER and PR should be routinely quantified in LGSSs by immunohistochemical methods.

Clear cell carcinoma of the uterine cervix: pathology and prognosis in surgically treated stage IB-IIB disease in women not exposed in utero to diethylstilbestrol.

OBJECTIVE: The purpose of this research was to compare the clinical behavior, pathology findings, and prognosis of surgically treated FIGO stage IB-IIB clear cell carcinomas of the cervix with those of squamous cell carcinomas and non-clear cell adenocarcinomas. METHODS: Fifteen patients with clear cell adenocarcinomas of the cervix (8 FIGO stage IB, 7 FIGO stage IIB) were reviewed. The control group consisted of 444 squamous cell carcinomas and 59 non-clear cell adenocarcinomas. None of the patients had a history of in utero exposure to diethylstilbestrol. All patients underwent radical abdominal hysterectomy with systematic pelvic lymphadenectomy. All specimens were processed as serial giant frontal sections. The mean follow-up in the clear cell group was 83 (13-182) months. Statistical analysis was done with contingency tables, chi(2) tests, and Fisher's exact test. RESULTS: Twelve of the fifteen clear cell carcinomas (80%) were endophytic and tended toward deep cervical infiltration. Clear cell carcinomas extended to the uterine corpus significantly more often than squamous cell and non-clear cell adenocarcarcinomas (P < 0.001). The rates of parametrial involvement and pelvic lymph node involvement were 40 and 47%, respectively. Four patients (27%), all with positive pelvic nodes, developed recurrences an average of 14 (4-48) months after initial therapy. The extrapelvic sites of relapse were the lung, liver, and bone. Clear cell carcinomas had a worse 5-year survival rate (67%) than squamous cell carcinomas (80%) and non-clear cell adenocarcinomas (77%) but this was not statistically significant (P = 0.6). No significant differences were seen for age, growth pattern, parametrial and vaginal involvement, parametrial and pelvic lymph node metastases, frequency of recurrent disease, and time to first recurrence. CONCLUSION: The clinicopathologic findings and prognosis of surgically treated patients with stage IB-IIB clear cell carcinomas without exposure to diethylstilbestrol in utero are similar to those of patients with squamous cell carcinomas and non-clear cell adenocarcinomas.

The tumor-associated shift in immunoglobulin G1/G2 is expressed at the messenger RNA level of peripheral blood B lymphocytes in patients with gynecologic malignancies.

BACKGROUND: Previously, it could be demonstrated that human patients with malignant diseases of various tissues exhibited characteristic and highly significant changes in the serum patterns of immunoglobulin (Ig)G subclasses, consisting of a decrease in IgG1 and an increase in IgG2 relative to total IgG. The aim of the current study was to determine whether this phenomenon was detectable at the level of IgG-producing B lymphocytes. METHODS: Using a competitive reverse transcriptase polymerase chain reaction specific to IgG1 and IgG2, the gene expression of these 2 IgG subclasses in peripheral B cells from 10 patients with carcinomas of various sites within the female reproductive tract and 10 healthy controls was quantitatively determined, in parallel with the concentrations of the respective serum proteins. RESULTS: Absolute levels of IgG subclass messenger ribonucleic acid (mRNA) showed a slight but not significant decrease in IgG1 and an increase in IgG2 in patients with gynecologic malignancies. However, the ratio of IgG1 to IgG2 expression showed a highly significant (P < 0.001) decrease in tumor patients compared with healthy controls, and corresponded to the change in the ratio of IgG1 to IgG2 serum proteins. CONCLUSIONS: These data suggest that the shifts in the serum patterns of IgG1 and IgG2 observed in patients with gynecologic malignancies are due to irregular biosynthesis of these IgG subclasses at the B-cell level.

Adaptative intima fibrosis in blood vessels in cervical carcinomas after preoperative cytotoxic chemotherapy.

Angiogenesis is an important component of tumor growth. After preoperative cytotoxic chemotherapy, tumor blood vessels of a large caliber become increasingly tortuous and their lumens narrow. The narrowing of the vessel lumens results from fibrosis of the intimal layer, which is called adaptative intimal fibrosis (AIF). We describe AIF in three patients with cervical cancer after a complete or partial response to preoperative cytotoxic chemotherapy. Two patients with no residual disease in the surgical specimen had severe AIF and are free of disease at 12 and 124 months. The patient with residual disease had only moderate AIF and developed a recurrence. AIF has not been described in cervical cancer. Our findings suggest that AIF may be a morphologic correlate of tumor regression following preoperative cytotoxic chemotherapy.

Chemotherapy versus radiotherapy versus observation for high-risk cervical carcinoma after radical hysterectomy: A randomized, prospective, multicenter trial.

BACKGROUND: Adjuvant treatment modalities after radical hysterectomy have long been used in an attempt to eradicate microscopic tumor residuals in patients at high risk for recurrence. However, it has not been clearly demonstrated that adjuvant radiation, adjuvant chemotherapy, or both improve the outcome. To evaluate the effect of adjuvant treatment in patients with high-risk cervical cancer after radical hysterectomy, the Austrian Gynecologic Oncology Group conducted a prospective, randomized, multicenter clinical trial between 1989 and 1995. MATERIAL AND METHODS: Seventy-six patients with stage IB-IIB cervical cancer treated with radical hysterectomy with pelvic lymph node metastases and/or vascular invasion randomly received adjuvant chemotherapy (400 mg/m2 carboplatin, and 30 mg bleomycin), standardized external pelvic radiation therapy, or no further treatment. RESULTS: After a median follow-up of 4.1 years (range, 2-7) there were no statistically significant differences (P = 0.9530) in disease-free survival among the three treatment arms. CONCLUSION: The data suggest that adjuvant chemotherapy or radiation do not improve survival or recurrence rates in high-risk cervical cancer patients after radical hysterectomy. The most important treatment for these patients seems to be radical abdominal hysterectomy with systematic pelvic lymphadenectomy.

Management and prognosis of primary fallopian tube carcinoma. Austrian Cooperative Study Group for Fallopian Tube Carcinoma.

We retrospectively analyzed 143 women treated in 28 departments from 1980 to 1995, to study the impact of prognostic factors in primary carcinoma of the fallopian tube. Further aims of the study were to evaluate the treatment of fallopian tube carcinoma in Austria. Staging of disease was done according to the modified FIGO system, and grading according to the criteria suggested by Hu et al. The mean age of the patients was 62.5 years. Sixty (42%) tumors were found to be in stage I, 28 (19%) in stage II, 38 (27%) in stage III, and 17 (12%) in stage IV. Radical resection was achieved in 102 (71%) patients. In 122 (85%) women surgery involved removal of the uterus, the adnexa, and/or the omentum or lymph nodes. Postoperatively patients underwent adjuvant therapy consisting of either irradiation (n = 40; 28%) or chemotherapy (n = 70; 49%); 33 women (23%) did not receive any treatment after surgery. The 5-year survival rate for all stages of disease was 43%. The 5-year survival rate was 59% for stages I and II and 19% for stages III and IV. FIGO stage, histologic grading and residual tumor showed an independent prognostic impact in multivariate analysis.

Consolidation radiotherapy after carboplatin-based chemotherapy in radically operated advanced ovarian cancer.

OBJECTIVE: The aim of the study was to evaluate the effect of additional radiotherapy after chemotherapy on the relapse-free and overall survival rates of patients with advanced ovarian cancer. METHODS: Between 1985 and 1992 64 patients with radically operated ovarian cancers (4 stage IC, 2 stage II, 54 stage III, and 4 stage IV) were enrolled in a randomized study. Radical surgery comprised total abdominal hysterectomy and bilateral salpingo-oophorectomy, omentectomy, and pelvic and paraaortic lymphadenectomy. All patients received adjuvant chemotherapy with carboplatin IV 400 mg/m2, epirubicin IV 70 mg/m2 on day 1 and prednimustine orally 100 mg/m2 on days 3 to 7 at 1-month intervals. Thirty-two patients without residual disease were randomized to whole abdominal radiation (30 Gy, administered over 4 weeks). An additional 21.6 Gy were delivered to the pelvis and 12 Gy to the paraaortic region up to the diaphragm for total doses of 51.6 and 42 Gy, respectively. Cancer-related survival was calculated with the Kaplan-Meier and Cox proportional hazards methods. RESULTS: The relapse-free and overall survival rates of patients who received adjuvant chemoradiotherapy were significantly higher than those of patients who received adjuvant chemotherapy only (68% vs 56% at 2 years and 49% vs 26% at 5 years, P = 0.013, and 87% vs 61% at 2 years and 59% vs 33% at 5 years, P = 0.029). The differences were most pronounced in patients with stage III disease (77% vs 54% at 2 years and 45% vs 19% at 5 years, P = 0. 0061, and 88% vs 58% at 2 years and 59% vs 26% at 5 years, P = 0. 012). Toxicities were acceptable. CONCLUSION: Sequential combination of platinum-based chemotherapy with open-field abdominal radiotherapy is a promising adjuvant regimen for patients with advanced ovarian cancer.

Lymphadenectomy in primary carcinoma of the Fallopian tube.

OBJECTIVE: The bad prognosis of primary carcinoma of the Fallopian tube is ascribed to early lymphogenous metastasis. Due to the rarity of cases, there exist only few and divergent results on the importance of lymph node metastasis in the relevant literature. Thus, our study aimed at detecting the incidence of lymph node metastases and their influence on overall survival, as well as at evaluating the therapeutic effect of radical lymphadenectomy. METHODS: We studied 158 cases of primary carcinoma of the Fallopian tube in a retrospective multicenter analysis. Group I (n = 38) consisted of patients who were subjected to radical pelvic and para-aortic lymphadenectomy in addition to total abdominal hysterectomy, bilateral adenectomy and omentectomy. The control group II (n = 71) underwent the same surgical procedures but without radical lymphadenectomy. Patients who received post-operative irradiation (n = 49) were excluded from the study. RESULTS: On average, 38 lymph nodes (range 12-68) were extirpated. In group I 42.1% of the cases showed lymph node metastases. Lymphatic dissemination was observed only after the carcinoma had spread beyond the organ (intraabdominal stage II); the incidence of lymph node metastases rose significantly (P = 0.02) with growing intraperitoneal tumour masses. Pelvic and para-aortic metastases occur simultaneously. Overall survival with tumour of equal size is markedly, but not significantly reduced (P = 0.18) if the lymph nodes are involved. If, however, radical lymphadenectomy is performed (group I) the median survival time increases to 43 months (95% confidence-interval 20-66), compared with 21 months (95% confidence-interval 10-32) in group II (P = 0.095). CONCLUSION: Correct staging is obtained only on the basis of pelvic and para-aortic lymphadenectomy. Radical lymphadenectomy in tumours of equal size may markedly prolong survival.

Prognostic factors in patients with carcinoma of the uterine cervix treated with external beam irradiation and IR-192 high-dose-rate brachytherapy.

PURPOSE: Prognostic factors in cancer of the cervix for patients treated with external beam irradiation (EBR) and low-dose-rate (LDR) brachytherapy have been characterized. However, despite the increasing use of high-dose-rate (HDR) intracavitary placements (ICP), few studies with adequate follow-up have analyzed prognostic factors. This study investigates pretreatment and treatment factors for their correlation with treatment outcome after EBR and HDR-ICP. METHODS AND MATERIALS: Between September 1985 and December 1994, 181 patients with carcinoma of the cervix FIGO stages IB-IV received EBR and HDR brachytherapy. Hemoglobin (Hb) levels were maintained above a level of 11 g/dl during the treatment by transfusion. Patient age ranged from 34 to 84 years (median: 66). The median follow-up time for patients at risk is 69 months (range: 23-140). Pretreatment and treatment parameters analyzed to determine their prognostic value included age, FIGO stage, tumor size, tumor type and grade, pretreatment Hb level, number of HDR-ICP, total dose from HDR-ICP, overall dose to point A, and overall treatment time. Also evaluated was the prognostic value of enlarged lymph nodes noted on pretreatment CAT scan of the abdomen and pelvis. Endpoints studied in uni- and multivariate analyses were disease-specific survival (DSS), freedom from disease (FFD), pelvic control (PC), and probability of distant metastases (DM). RESULTS: At 5 years the DSS, FFD, and PC rates for all patients were 60%, 58%, and 67%, respectively. The 5-year FFD by stage was: IB: 94%; II: 63%; IIIB: 43%; and IV: 0%. The PC rates were 94%, 66%, 59%, and 0%, respectively. In univariate analysis the prognostic factors identified for FFD were FIGO stage, tumor size, initial Hb level, and enlarged pelvic and/or paraaortic nodes (all: p < 0.0001). Age was inversely correlated with outcome (p = 0.0081). The 5-year FFD rates for tumors (< 3, > or = 3 < 6, > or = 6 cm) were 97%, 65%, and 24%; patients with initial Hb levels < or = 11g/dl had a FFD of 26% versus 69% for patients with levels > 11g/dl; and those with pelvic and/or paraaortal nodes > or = 1 cm had a survival of 32% versus 68% in patients with negative readings. The same factors were also prognostically significant for DSS, PC, and DM. Patients with persistent disease or pelvic failures had a significantly higher incidence of DM than patients in whom pelvic disease was controlled (p < 0.0001).Histological and treatment parameters including overall treatment time were not of prognostic significance for any of the endpoints studied. In multivariate analysis tumor size was the most powerful parameter for DSS, FFD, PC (p < 0.0001) and DM (p = 0.0001), followed by low initial Hb level (DSS: p = 0.0004, FFD: p = 0.0009, PC: p = 0.0012, DM: p = 0.0265), and enlarged pelvic and/or paraaortic nodes which were predictive for DSS (p = 0.0210) and DM (p = 0.0011). CONCLUSION: This study confirms that prognostic factors for patients treated with HDR brachytherapy are similar to those reported in previous series that employed LDR brachytherapy. The significance of tumor size, pretreatment Hb level, and enlarged pelvic and/or paraaortic lymph nodes on CAT scan over FIGO stage of disease were demonstrated. Future prospective trials should be undertaken to confirm the validity of these factors and to elucidate their therapeutic implications.

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.

A 15-year overview of management and prognosis in primary fallopian tube carcinoma. Austrian Cooperative Study Group for Fallopian Tube Carcinoma.

143 women treated in 28 departments from 1980 to 1995 were retrospectively analysed to study the impact of prognostic factors in primary carcinoma of the fallopian tube. The mean age of the patients was 62.5 years. Sixty (42%) tumours were FIGO stage I, 28 (20%) stage II, 38 (27%) stage III, 17 (12%) stage IV. Complete radical resection was achieved in 102 (71%) patients. In 122 (85%) women, surgery involved removal of the uterus, the adnexa, and/or the omentum or lymph nodes. Postoperative therapy consisted of either irradiation (n = 40; 28%) or chemotherapy (n = 70; 49%); 33 women (23%) did not receive any treatment after surgery. The 5-year survival rate for all cases was 43%. The 5-year survival rate was 59% for stages I and II and 19% for stages III and IV (P < 0.00001). FIGO stage, histological grade and presence of residual tumour had an independent prognostic impact in multivariate analysis. In order to investigate the role of p53 in primary fallopian tube carcinomas, we analysed the immunohistochemical expression of p53 protein regarding survival and FIGO stage in 63 patients (44%). No statistical significance was observed.