Local recurrences following mastectomy: support for the concept of tumor dormancy.

BACKGROUND: Local or regional recurrence of breast cancer occurs in 5%-30% of patients treated by Halsted radical or modified radical mastectomy. Lag time between treatment and recurrence varies widely, and it is not known whether the recurring tumor grows at a constant growth rate or at a more rapid rate after a period of tumor dormancy. PURPOSE: This study was undertaken to discriminate between the above-mentioned hypotheses, i.e., determine whether a tumor that recurs after mastectomy grows at a constant rate or whether it grows rapidly following a period of tumor dormancy. METHODS: A series of 122 patients with local recurrence as a first event after mastectomy for resectable breast cancer was evaluated. We measured the diameter of the recurring tumor (Dr) in each patient and calculated the diameter that the recurring tumor could have reached at the immediately preceding physical examination (Dpe), when no local relapse had yet been detected, by assuming an exponential growth during the treatment-free interval. For patients who had a calculated diameter Dpe that was large enough to have been detected at the previous examination, we assumed that a tumor 5 mm in diameter had been mistakenly missed, and the expected corresponding tumor diameter at the time of detection (Drc) was calculated. Finally, the minimum growth rate (mGR) consistent with the sequence "no detection-->recurrence of diameter Dr" was obtained by assuming an exponential growth from the tumor volume corresponding to a diameter 1 mm less than the diameter detection threshold. RESULTS: A wide overlap between Dr and Dpe values was observed. Seventy-two (59%) of 122 Dpe values were larger than the minimum Dr; 18 (15%) were even larger than the median Dr value. The difference between expected and observed detection rates was highly significant (P < .0001). Furthermore, when treatment-free intervals were longer than 4 years, the difference between median Dr and median Dpe values failed to reach statistical significance. The Drc values were significantly lower than the related Dr values, while the mGR values were significantly higher than the corresponding growth rates (paired sample t test: P < .001). CONCLUSION: This study provides evidence that the hypothesis of uninterrupted constant growth of locally recurring breast tumors should be rejected, as it implies a statistically significant departure from observed data. Our results suggest that a period of tumor dormancy followed by more rapid growth could provide an alternative and more reasonable description of tumor recurrence.

Adjuvant chemotherapy with doxorubicin plus cyclophosphamide, methotrexate, and fluorouracil in the treatment of resectable breast cancer with more than three positive axillary nodes.

To improve current adjuvant results in high-risk breast cancer, in February 1982 we activated a prospective randomized trial using both intravenous cyclophosphamide, methotrexate, and fluorouracil (CMF) and Adriamycin (doxorubicin; Farmitalia-Carlo Erba, Milan, Italy) involving patients with resectable mammary carcinoma and more than three positive axillary lymph nodes. The objective of the study was to assess the effectiveness of four courses of Adriamycin followed by eight courses of CMF versus two courses of CMF alternated with one course of Adriamycin for a total of 12 courses. All drug courses were recycled every 3 weeks. Rather than temporarily reducing doses in the event of myelosuppression on the planned day of treatment, drug administration was delayed for 1 to 2 weeks. At a median follow-up of 59 months, treatment outcome was significantly superior for patients who received Adriamycin followed by CMF (Adriamycin----CMF) than for those given alternating regimens (CMF/Adriamycin). The 5-year relapse-free survival was superior post-Adriamycin----CMF (61%) compared with post-CMF/Adriamycin administration (38%; P = .001). The corresponding figures for the 5-year total survival were 78% and 62%, respectively (P = .005). The benefit of Adriamycin----CMF was observed in all patient subsets. Treatment was fairly well tolerated, and we documented only one case of fatal congestive heart failure in a patient who received postoperative irradiation to the left breast in addition to Adriamycin. Present findings indicate that in women with extensive nodal involvement, Adriamycin----CMF yielded superior results compared with CMF/Adriamycin.

Cyclophosphamide, methotrexate, and fluorouracil with and without doxorubicin in the adjuvant treatment of resectable breast cancer with one to three positive axillary nodes.

In the attempt to improve current adjuvant results in patients with one to three positive axillary lymph nodes, in November 1981 we activated a prospective randomized study to assess the effectiveness of intravenous (IV) cyclophosphamide, methotrexate, and fluorouracil (CMF) for 12 courses versus CMF for eight courses followed by Adriamycin (doxorubicin; Farmitalia Carlo Erba, Milan, Italy) for four courses. The 5-year results were evaluated in a total of 486 patients entered into the study up to December 1987. CMF chemotherapy was delivered IV for a total of 12 courses when given alone and for eight courses when followed by four courses of Adriamycin. All drugs were recycled every 3 weeks. Rather than temporarily reducing doses, drug administration was delayed for 1 to 2 weeks in the face of myelosuppression on the planned day of treatment. After a median follow-up of 61 months, no significant differences were evident between the treatment groups in terms of relapse-free (CMF 74% v CMF followed by Adriamycin 72%) and total survival (CMF 89% v CMF followed by Adriamycin 86%). Drug treatments were fairly well tolerated and devoid of life-threatening toxicity. Present results, which were not influenced by menopausal status, indicate that Adriamycin given after CMF failed to improve treatment outcome over CMF alone. However, the role of Adriamycin in an adjuvant setting remains to be further clarified. Considering the good 5-year results achieved in this study at the expense of minimal toxicity, full-dose CMF remains, at present, the adjuvant chemotherapy of choice for patients with one to three positive nodes.

Long-term cardiac sequelae in operable breast cancer patients given adjuvant chemotherapy with or without doxorubicin and breast irradiation.

PURPOSE: To investigate long-term cardiac sequelae associated with anthracycline use in adjuvant chemotherapy of patients with early breast cancer. PATIENTS AND METHODS: All 1,000 patients from three prospective trials of adjuvant chemotherapy containing doxorubicin (n = 637, median total dose of 294 mg/m(2)) or not containing the anthracycline (cyclophosphamide, methotrexate, and fluorouracil [CMF] regimen alone, n = 363) were analyzed for the relative incidence of congestive heart failure (CHF) and myocardial infarction (MI) during 14 years of follow-up. The 462 women continuously free of disease as of February 1996 were recalled, and 355 consented to undergo evaluation including 12-lead ECG and cardiac ultrasound with determination of left ventricular ejection fraction (LVEF) to assess the relative incidence of abnormalities in long-term survivors. RESULTS: Among the 1,000 patients, there were six cases of CHF and three cases of MI. Cumulative cardiac mortality accounted for 0.4% (doxorubicin-treated = 0.6%; CMF-treated = 0). Eighteen (5%) of the 355 patients undergoing cardiac evaluation after median 11 years of follow-up presented systolic dysfunction as defined by pathologic (< 50%, n = 8) or borderline (50% to 55%, n = 10) LVEF. Systolic dysfunction was higher in doxorubicin-treated (15 of 192; 8%) than in CMF-treated patients (three of 150; 2%). Breast irradiation had a significant impact on the occurrence of early CHF (four of 116; 3%), but not on systolic dysfunctions. CONCLUSION: At longer than 10 years of follow-up, the use of doxorubicin at a total dose commonly applied in regimens of adjuvant chemotherapy does not lead to cardiac clinical sequelae that counter-balance the benefit of treatment in patients with operable breast cancer who may be cured of their disease.

Primary chemotherapy in operable breast cancer: eight-year experience at the Milan Cancer Institute.

PURPOSE: Primary chemotherapy was administered to patients with tumors that measured > or = 2.5 cm in largest diameter to decrease the size of the primary tumor and allow for effective local and distant control while avoiding mastectomy. PATIENTS AND METHODS: Two prospective nonrandomized studies were performed that used different regimens of primary chemotherapy followed by breast-sparing surgery in the presence of objective tumor remission. Additional postoperative chemotherapy was given to women at high risk of disease relapse. The median follow-up duration was 65 months. RESULTS: A total of 536 assessable patients were enrolled, and the main characteristics were fairly comparable between the two trials. Following primary chemotherapy, 85% of patients could be subjected to breast-sparing surgery; in 14 patients (3%), surgical specimens failed to show any residual neoplastic cell. In the final multivariate analysis, the histologically assessed extent of axillary node involvement (P < .001), as well as degree of response to primary chemotherapy (P = .034), represented the significant variables able to influence 8-year relapse-free survival. In women subjected to a breast-conserving approach, the cumulative risk of local relapse as first event alone was 6.8% (95% confidence interval, 3.9% to 8.8%). CONCLUSION: Current findings indicate that primary chemotherapy can be safely administered in women with large tumors (>5.0 cm) and can allow breast-sparing surgery in a high fraction of patients (62%). However, to assess effectively the worthiness of this approach on long-term results, properlyconceived large randomized studies with newer and more effective drug regimens are warranted.

Efficacy, toxicity, and applicability of high-dose sequential chemotherapy as adjuvant treatment in operable breast cancer with 10 or more involved axillary nodes: five-year results.

PURPOSE: To assess the efficacy, toxicity, and applicability of high-dose therapy administered as adjuvant initial treatment to women with breast cancer with extensive nodal involvement. PATIENTS AND METHODS: Sixty-seven patients with stage II to III breast cancer involving > or = 10 axillary nodes received a novel high-dose sequential (HDS) regimen, including the high-dose administration of three non-cross-resistant drugs (cyclophosphamide, methotrexate, and melphalan) given within the shortest interval of time as possible with hematologic and nonhematologic toxicity. RESULTS: Sixty-three patients completed the program as planned, one patient died of acute toxicity, and three patients were switched to standard-dose adjuvant therapy. After a median follow-up duration of 48.5 months and a lead follow-up of 78 months, actuarial relapse-free survival for all 67 registered patients is 57% and overall survival is 70%, respectively. Comparison with a historical control group of 58 consecutive patients showed a significantly superior rate of freedom from relapse for the HDS-treated group (57% v 41%, respectively), in particular when two subgroups of patients, more homogeneous for their number of involved nodes, were compared (65% v 42%). Overall, treatment was of short duration (median, 70 days), required a median of 32 days of hospital stay, and was associated with only a few severe side effects (the most distressing being oral mucositis after melphalan therapy). CONCLUSION: HDS therapy emerges as an effective and applicable regimen, whose major toxicity was occasional. Final assessment of its value in a randomized, multicenter trial is presently underway.

Adjuvant CMF for node-negative and estrogen receptor-negative breast cancer patients.

From December 1980 to September 1985, a total of 90 eligible patients with stage T1-3a, node-negative, and estrogen receptor-negative (less than or equal to 10 fmol/mg of cytosol protein) tumors were entered into a randomized study to assess the effectiveness of adjuvant intravenous (IV) cyclophosphamide, methotrexate, and fluorouracil (CMF) in a subset of patients at high risk of early disease relapse. High values of [3H]thymidine labeling index were documented in two thirds of 62 assessed specimens from the patient population, and one half of the patients had histologically undifferentiated tumors. Patients were allocated to either local-regional modality alone (control group, 45 women) or to CMF (45 patients) after surgery. A full dose of CMF (600 mg/m2 each of cyclophosphamide and fluorouracil, and 40 mg/m2 of methotrexate) was administered IV on day 1, and then repeated every 3 weeks for a total of 12 treatments. After a median follow-up of 80 months, the 7-year results confirmed the superiority of adjuvant CMF compared to local-regional modality alone (relapse-free survival 85% vs 42%, P = .0001; total survival 86% vs 58%, P = .006). A benefit from adjuvant CMF was observed in all subgroups, and the rates of both local-regional and distant failure were decreased. Treatment was fairly well tolerated and devoid of life-threatening toxicity. Present results confirm our previous observation concerning the dismal prognosis of node-negative and estrogen receptor-negative breast cancer patients as well as the beneficial effect of adjuvant chemotherapy in this selected subset.

T3b-T4 breast cancer: factors affecting results in combined modality treatments.

Two hundred and seventy-seven consecutive patients with T3b-T4 breast cancer referred to the Milan Cancer Institute between 1973 and 1980 were treated with a combined modality approach. Chemotherapy (CT) consisted of AV, i.e. adriamycin (60-75 mg/m2 day 1) and vincristine (1.2 mg/m2 days 1 and 8) and was given for three to four cycles prior to local regional modality. Local-regional treatment consisted of either radiotherapy (RT) in 198 patients or surgery (S) in 79 women. Additional chemotherapy was then administered to a total of 205 patients. In the absence of distant metastases, frequency of good local control was significantly inferior in patients given CT + RT (63.9 per cent) compared to those treated with CT + RT + CT (75.4 per cent) and CT + S + CT (82.3 per cent, P = 0.033). Also freedom from progression (FFP) and overall survival (SURV) were significantly superior in the groups receiving more prolonged chemotherapy treatment compared to patients treated with CT + RT (FFP: P less than 0.0001; SURV: P = 0.002). None of the variables examined was able to affect the response rate, while axillary nodal status and tumor size played a major role in the duration of FFP and SURV. Our findings indicate that a more aggressive treatment is needed to improve current results in this stage of disease. To overcome the problem of local-regional recurrence, treatment should probably begin with cytoreductive surgery followed by postoperative radiotherapy in all patients with the exception of those having inflammatory carcinoma. Systemic treatment should then be delivered to control distant micrometastases.

Sequential Adriamycin and CMF in Metastatic Breast Cancer.

PURPOSE: To evaluate the clinical activity of a sequential treatment with Adriamycin followed by CMF (cyclophosphamide, methotrexate, fluorouracil) and the relative therapeutic contribution of the two drug regimens given at full conventional doses in metastatic breast cancer. PATIENTS AND METHODS: From August 1990 to February 1993, 44 patients with advanced breast cancer previously untreated with chemotherapy entered the study. Treatment consisted of the intravenous administration of Adriamycin (75 mg/m² on day 1 every three weeks) for four cycles followed by intravenous CMF (cyclophosphamide, 600 mg/m²; methotrexate, 40 mg/m²; fluorouracil 600 mg/m²) on days 1 and 8 every four weeks for four total courses. RESULTS: In 41 evaluable patients, four cycles of full-dose Adriamycin were able to achieve an overall response rate of 75%, including 17% complete remissions. Four cycles of CMF administered after Adriamycin were able to increase tumor response in 64% of evaluable cases. At the end of the sequential treatment program, 78% of 41 patients achieved an objective remission and in 30% of them a clinical complete response was documented. Main side effects, i.e., leukopenia and gastrointestinal disturbances, were moderate and short-lasting. One patient died because of acute myocardial infarction. CONCLUSION: In untreated metastatic breast cancer patients, the sequential administration of Adriamycin and CMF is highly effective at the expense of a moderate toxicity profile that allows high-dose intensity of both drug regimens. CMF treatment after upfront Adriamycin is able to exert a further therapeutic advantage.

Adjuvant and neoadjuvant treatment of breast cancer.

Treatment of early breast cancer has been revolutionized during the past 30 years and new data continue to refine our knowledge of systemic treatments for this stage of disease. The updated worldwide overview has confirmed that, in terms of recurrence and survival, the balance of the known long-term benefits and risk favors some months of adjuvant polychemotherapy and/or a few years of tamoxifen for a wide range of patients. Both the overview and individual trials have shown that anthracycline-containing regimens can achieve additional reduction of the risk of disease relapse and death over cyclophosphamide, methotrexate, and fluorouracil (CMF)-like regimens. Paclitaxel-containing regimens appear promising, but require additional confirmation with longer follow-up. By contrast, controversy still exists on the role of high-dose chemotherapy in high-risk patients. Primary (neoadjuvant) chemotherapy is a new modality to treat large operable breast cancers and offers the possibility of breast conservation with treatment results at least similar to those achieved with classical adjuvant regimens. In the near future, newer agents and information gained on the role of prognostic and predictive factors will probably increase the effectiveness of adjuvant and neoadjuvant treatments.

Adjuvant chemotherapy after conservative surgery plus irradiation versus modified radical mastectomy. Analysis of drug dosing and toxicity.

In a cohort of 764 evaluable patients with primary breast cancer, we have compared the ability to deliver full doses of adjuvant chemotherapy in two patient groups: one undergoing conservative breast surgery plus irradiation and the other having modified radical mastectomy as primary treatment for the cancer. We have also analyzed the toxicities of the concurrent radiation and chemotherapy. The group having irradiation had significantly more moderate leucopenia, which caused a short delay (median, three weeks) in the overall time necessary to complete the planned chemotherapy. However, among those patients who completed the planned chemotherapy cycles, the fraction who received more than 85 percent average drug doses was 96 percent or higher in all but one small subgroup. Interaction between the irradiation and chemotherapy caused mild breast skin reactions in 42 percent of patients so analyzed and worse reactions in 12 percent. When follow-up tracings were performed, mild electrocardiogram abnormalities occurred in 19 percent of patients, apparently because of the irradiation. We conclude that intravenous adjuvant chemotherapy, as administered in this study, can be delivered as intensely with conservative primary treatment as after mastectomy and that toxicity is mild, rarely requiring intervention or treatment discontinuation.

Detection of Lewis(a) antigen in sera of ovarian carcinoma patients by MOv2-MOv8 double-determinant radioimmunoassay.

The monoclonal antibodies MOv2 and MOv8, raised against ovarian carcinoma, were found to be directed against two non-crossreacting epitopes expressed on the same molecule. Immunochemical analysis of the MOv8 recognized epitope showed that the Le(a) oligosaccharide, or commercial anti-Le(a) MAb, but not the anti-Le(b) MAb, prevented Ov8 binding to the reference target cell line (SW626), indicating that it is carried by the Le(a) antigen. Since we previously reported that MOv2 also recognises the Le(a) antigen, these data suggest that Mov8 and Mov2 were directed against different epitopes on the same oligosaccharide chain. Bearing in mind the knowledge of the biochemical nature of the monoclonal antibody recognized epitopes (CaMOv2 and CaMOv8), the presence of the circulating molecules recognized by them was analyzed by double determinant immunoradiometric assay (DDIRMA) in 103 sera from ovarian carcinoma patients. Patients with clinical evidence of the disease (ED) with MOv2 and MOv8 reactive and negative tumors had sera reactivity in 67% and 19% respectively. Also, 26% of the patients with no clinical evidence of disease (NED) had positive sera. When we investigated the relationship between MOv2-MOv8 DDIRMA sera positivity and red blood cells (RBC) Lewis phenotype, a strong correlation was found between the Le(a)+ phenotype and DDIRMA sera reactivity in healthy donors (6/6) and in ovarian carcinoma patients (9/10) whatever their clinical condition. No Le(a)- healthy donors gave evidence of MOv2-MOv8 reactive sera. In contrast, 33% and 57% of the sera from ED carcinoma patients with respectively Lea-b+ and Lea-b- phenotype were positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Intermediate doses of cyclophosphamide alone or following adriamycin in advanced breast cancer. A pilot study.

Cyclophosphamide (CTX) is an active drug in breast cancer and presents a well-established dose-response relationship. To explore further this relationship, the present pilot study investigated the therapeutic efficacy of cyclophosphamide at intermediate dose in two groups of untreated patients with advanced breast cancer. Nine women received the drug alone at 3-4 g/m2 i.v. every 2 weeks for a total of three doses. The same dose schedule was also given to 11 women following the administration of four cycles of Adriamycin, at 75 mg/m2 i.v. every 3 weeks. We documented one partial remission in untreated women and four partial responses in Adriamycin-treated patients. The major toxicity was represented by leukopenia and neutropenia. Myelosuppression was relevant but of short duration, and the use of G-CSF appeared useful in controlling this side effect. In spite of the high dose intensity of the present cyclophosphamide dose schedule (9 g/m2 in 4 weeks), i.e., almost three times superior to that conventionally employed, present results do not suggest its superiority over the current chemotherapeutic regimens utilized in advanced disease.

First-line chemotherapy with intraperitoneal cisplatin and intravenous cyclophosphamide in ovarian carcinoma. A preliminary report.

Between August 1982 and October 1986, the feasibility and activity of five cycles of intraperitoneal (i.p.) cisplatin (CDDP) (90 mg/m2 in 6 h dwelling) and i.v. cyclophosphamide (600 mg/m2) were studied in 24 previously untreated patients with ovarian carcinoma having small or no residual disease after cytoreductive surgery. Six patients (25%) had local complications requiring catheter removal before the end of therapy. Fifteen of the 21 patients (71%) evaluable for activity achieved or maintained a pathologic complete remission. The median disease-free survival was 29+ months (range 18-58+ months). Three patients with tumor progression (two patients previously without evidence of disease, and one patient with minimal residual disease), and three partial responders were documented by laparotomy at the end of therapy. Two patients who achieved pathologic complete response relapsed at 20 and 36 months. All treatment failures (eight cases, 38%) occurred in the peritoneal cavity. Since patients were selected for having the most favorable tumor characteristics to benefit from i.p. treatment, our findings may cast some doubt on the actual contribution of i.p. CDDP at a dose of 90 mg/m2 in the treatment of patients with ovarian carcinoma and small residual disease in the peritoneal cavity.

Cisplatin and cyclophosphamide in advanced ovarian carcinoma: activity and toxicity of an ambulatory regimen.

Chemotherapy with cisplatin (CDDP, 90 mg/m2) and cyclophosphamide (CTX, 600 mg/m2) was administered to 54 consecutive patients with advanced epithelial ovarian cancer (37 stage III and 17 stage IV). In 51 patients, surgery was performed prior to chemotherapy. Of the 37 stage III patients, 13 had only minimal residual disease after surgical debulking. The overall response rate was 69%, with 44% patients achieving clinical (cCR; n = 2) or pathological (pCR; n = 20) complete response. Median follow-up and overall survival time was 26 months, and median CR duration was 30 months. CR was achieved in 6 of 14 patients (43%) who were partial responders after five cycles of chemotherapy and had continued treatment for three to five more cycles. Severe bone marrow toxicity or renal function impairment was never observed, but eight patients presented peripheral signs of dose-related neurotoxicity. These findings indicate that CDDP and CTX in combination are an effective treatment for patients with advanced ovarian carcinoma, and can be administered with tolerable toxicity. In selected cases, prolonged chemotherapy administration can result in durable complete remissions.

Aminoglutethimide in postmenopausal breast cancer refractory to multiple hormonal and cytostatic treatments.

Eighty-seven consecutive patients with metastatic breast cancer were treated with aminoglutethimide plus hydrocortisone. All patients were postmenopausal and had progressive disease following prior chemotherapy and endocrine therapy. Eighty-five women were evaluable for drug response. One patient showed complete remission and 14 patients partial response, for an overall response rate of 17%. The median duration of response was 11+ months. The response rate was highest in the presence of soft tissue involvement (36%). The most common side effects were transient skin rash, lethargy, and dizziness. Two patients discontinued treatment because of cutaneous allergy. Aminoglutethimide can be considered a moderately active agent when utilized as second- or third-line hormonal therapy.

Antiemetic activity of metoclopramide versus alizapride during cancer chemotherapy.

A prospective randomized study was conducted to compare the antiemetic efficacy of metoclopramide (MCP) versus its recent derivative alizapride (ALZ) in patients undergoing cancer chemotherapy. Both drugs were given at a dose of 2 mg/kg i.v. push for 5 doses. A positive response was defined as absence of nausea or emesis, or moderate nausea with one or two emeses per day. Eighty-two patients were evaluable. Forty-two received MCP and 40 received ALZ. A positive response was observed in 54% MCP-treated and 41% ALZ-treated patients. Neurologic toxicity, mainly extrapyramidal disturbances, was the most remarkable adverse side effect; it occurred more frequently in the MCP-treated group (31%) than in the ALZ-treated group (17%). Both drugs were found to be more effective in previously untreated patients and when employed together with steroids. MCP was more effective (52% positive response) than ALZ (41% positive response) in cisplatin-treated patients. To better control drug-induced vomiting, we believe that future trials should evaluate slow i.v. infusion of antiemetic agents and their combination with dexamethasone.

Timing of surgery and the role of cytoreductive chemotherapy in patients with advanced ovarian carcinoma.

We retrospectively selected 27 consecutive patients with advanced ovarian carcinoma (15 stage III, 11 stage IV and 1 relapse) who had an unresectable intraabdominal tumor at presentation and prospectively evaluated the overall treatment outcome. Patients were initially treated with chemotherapy consisting of cisplatin-containing regimens in 20 cases, adriamycin and cyclophosphamide in 5, and melphalan in 2. Treatment was continued until maximal tumor response or progression. Following a median of 6 cycles of chemotherapy, all patients underwent debulking surgery. Six women were without evidence of disease and 13 had minimal residual disease after surgery, for an overall 70% rate of optimal debulking. Patients with evidence of disease at laparotomy were treated with 5 additional cycles of chemotherapy, and response was then assessed at laparotomy except for patients with progressive disease. Nine (33%) patients were pathologic complete responders at the end of the entire treatment program. Overall median survival time was 26 months, with a median relapse-free survival of 33 months. Tumor responses were not associated with any particular chemotherapy regimen. The results achieved in this series of patients together with the data from the literature suggests that use of a cytoreductive chemotherapy of short duration has the potential of increasing the rate of optimal debulking surgery. Furthermore, it may contribute to a better disease control in women with bulky ovarian carcinoma compared to the present strategy, which consists of surgery followed by chemotherapy.

Mitomycin C and vinblastine in advanced refractory breast cancer.

A combination of mitomycin C and vinblastine was administered as salvage treatment in 44 patients with heavily pretreated refractory breast cancer. Response rate was 23% (10 of 44) including one complete response of lung metastases. The highest response rate was seen in intrathoracic localizations (45%). Median duration of response was 6.5 months (range, 3+-17+). Treatment was generally well tolerated, and only 25% of patients developed nausea and vomiting. Neurologic toxicity was represented by paresthesia (8 patients) and constipation (one patient). Mild leukopenia was observed in 30 of 172 treatment cycles, but it exceeded grade 2 in only 5 patients. Considering the good compliance of this regimen and the poor prognosis of patients with advanced refractory disease, the combination of mitomycin C plus vinblastine appears to be useful as salvage treatment for metastatic breast cancer.

Accuracy of the double contrast enema in evaluation of the abdominal diffusion of ovarian carcinoma.

The results of 103 double contrast enemas in 72 patients with ovarian carcinoma (stage III and IV) were compared with laparoscopic and/or laparotomic findings at comparable times. The evaluation of the validity of radiology in detecting the presence of abdominal disease showed an 84% overall accuracy, 75% specificity and 86% sensitivity. The accuracy in detecting signs of adhesion and parietal infiltration of the large bowel was 76.3%, due to the limited size of most of the lesions. Forty-seven of the 72 patients underwent a double contrast enema and laparoscopy during presurgical staging: accuracy in detecting lesions was the same for both examinations (80.4%). When double contrast enema and laparoscopy were used together in the evaluation of abdominal extension of the disease, the diagnostic accuracy rose to 93.6%.