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Background: To elucidate the role of second-look laparotomy in the management of ovarian cancer patients, were retrospectively reviewed our experience with this procedure in epithelial ovarian cancer patients., Patients and Methods: The hospital records of 617 patients with advanced ovarian cancer were reviewed. The 308 patients who underwent second-look laparotomy were followed from four to 18 years with a median follow-up of 12 years after start of primary chemotherapy., Results: Patients who achieved pathological complete response (PCR), microscopic partial response (PPR mic.), macroscopic partial response (PPR mac.), stable disease (PSD), and progressive disease (PPD) at second-look laparotomy had a median survival time of 149, 39.5, 24, 14, and eight months, respectively. Secondary surgical cytoreduction could be performed only in 101 patients with macroscopic persistent disease. The group of all patients with secondary tumor debulking had no survival advantage compared with the group of patients with PPR mac., PSD, and PPD, unable to have secondary cytoreduction. Patients left with no tumor after second-look laparotomy did not survive as long as patients who achieved PCR and PPR mic. at second-look laparotomy. Factors prolonging survival after second-look laparotomy included younger age, good pre-treatment performance status, smaller primary residual tumor size, longer interval between start of chemotherapy and second-look laparotomy, and the pathologically proven CR or PR mic., Conclusion: Second-look laparotomy appears to have a minor role in the routine management of ovarian cancer patients, especially in the context of the limited effectiveness of second-line therapy. This procedure should be limited to clinical treatment protocols to determine effectiveness of new agents.

Purpose: The introduction of platinum compounds and epipodophyllotoxins in combination with vincristine as induction chemotherapy in small-cell lung cancer (SCLC) was investigated in order to: (1) compare the efficacy of cisplatin with that of carboplatin in combination with teniposide and vincristine as inducers of remission over three cycles; (2) compare the toxicity pattern of carboplatin and of cisplatin when given in combination regimens; and (3) compare a chemotherapeutic regimen consisting of three alternating combinations with that of regimens consisting of four alternating combinations., Patients and Methods: From November 1985 to September 1991, 484 consecutive, previously untreated patients with SCLC, performance status 0-4, entered a three armed randomized trial with three cycles of cisplatin (arm I) or carboplatin (arm II) in combination with teniposide and vincristine alternating with three treatment blocks of cyclophosphamide, etoposide, lomustine and vincristine (block A), doxorubicin and vincristine (block B) and cisplatin, hexamethylmelamine and vindesine (block C) versus alternating treatment with block A, B and C (arm III)., Results: No difference in efficacy or toxicity was found between cisplatin and carboplatin at the present dosages. Induction chemotherapy with teniposide plus cisplatin or carboplatin did not result in higher complete response rates (objective response rates 63%, 72% and 65%, respectively) or in significantly greater toxicity, but overall survival was superior compared with the arm III (log-rank test, P = 0.02). The median survival difference was 7 weeks, and two year survival 15% versus 9%. The Cox regression analysis identified the arm III, poor performance status and elevated LDH as factors with statistically significant negative impact on survival., Conclusion: Cisplatin and carboplatin produced similar response and survival rates and similar toxicity. Induction with platinum and epipodophyllotoxins did not improve objective response rates, but significantly improved survival without increasing the toxicity.

Background: Recently, the ganglioside Fucosyl-GM1 (FucGM1) has been described as a possible new tumour marker for small-cell lung cancer (SCLC). FucGM1 has been detected in 75% to 90% of SCLC tumours by immunohistochemical analysis and in about 50% of sera from SCLC patients. Neuron-specific enolase (NSE) is a glycolytic enzyme which is expressed in the majority of SCLC tumours and patient sera., Patients and Methods: Sera from 156 patients with SCLC were analyzed for FucGM1 with a scintillation proximity assay (SPA), which is a simple and sensitive analysis. Sera were analyzed before the initiation of chemotherapy, and twenty patients were monitored during and after treatment. The concentration of FucGM1 was compared to the tumour marker NSE and related to clinical data and survival., Results: Sixty-three per cent of the patients were positive for FucGM1. The concentrations did not correlate with NSE or clinical data including stage of disease, organ site of metastases or ABO blood group status. Nor did the expression of FucGM1 correlate with survival. As a monitor of clinical response, a correlation was found in 8 out of 20 patients. Eighty-four per cent of the patients were positive for NSE; and 97% were positive for either FucGM1 or NSE., Conclusion: We conclude that FucGM1 does not have a clinical role as a tumour marker for patients with SCLC at diagnosis or during treatment.

Background: Radically excised ovarian cancers present an unsolved problem with regard to the value of routine second-look operation. This study presents the outcome of second-look operations in an effort to help elucidate this problem., Patients and Methods: Twenty-eight patients who underwent radical surgery for ovarian cancer stage IC-IIIA were given adjuvant chemotherapy with cyclophosphamide 500 mg/m2 i.v., adriamycin 40 mg/m2 i.v. and 5-fluorouracil 500 mg/m2 i.v., all administered on days 1 and 8 every 4 weeks until achievement of a cumulative adriamycin dose of 400 mg/m2. It was planned that second-look laparotomy would be performed 10-12 months after the primary operation., Results: Four of 28 patients (14.3%) had positive findings at second-look laparotomy. Two of these 4 patients had only microscopic disease, and after second-line chemotherapy including cisplatin one of them is clinically free of tumor 50 months after the primary operation. Two of 28 patients had clinical recurrences before the planned second-look operation. Four of the 22 patients (18.2%) with negative second-look operations developed recurrent disease within a median time of 12 months later. The 5-year survival rate for all 28 patients was 67%., Conclusion: Although a small group of patients may benefit from a strategy that includes delayed second-look operation, we conclude that this should not be a routine procedure in the management of patients who undergo radical surgery for ovarian cancer.

Background: Many ovarian cancer patients will after treatment of the recurrence with cisplatin based therapy enter phase I or II studies with new drugs. Lately, some new agents have shown activity., Materials and Methods: The review is based on phase II studies mainly and focuses on paclitaxel (taxol)., Results: A Canadian/European study of high (175 mg/m2) versus low dose (135 mg/m2), and short (3 hours) versus long (24 hours) infusion confirms the reported activity of paclitaxel in previously treated patients. The preliminary overall response rate in 286 evaluable patients is 18.5%. A dose effect exists regarding neuropathy and neutropenia, and a longer infusion duration results in a higher frequency of grade 4 neutropenia. In a phase III study comparing cisplatin 75 mg/m2 plus cyclophosphamide (750 mg/m2) or plus paclitaxel 135 mg/m2 over 24 hours, the paclitaxel-based combination gave a superior response rate (54% versus 33%) and statistically significant longer progression-free interval. The semisynthetic docetaxel (taxotere) gives an overall response rate of 32% (95% confidence interval 23%-43%). Skin toxicity and edema are dose-limiting factors. Gemcitabine has also shown activity in platinum-resistant patients with an overall response rate of 23% (95% CI 10%-40%)., Conclusions: The role of new drugs in first-line therapy remains to be seen. Further development of experimental work for screening and evaluation of new agents is needed.

In a randomized double-blind, cross-over trial of 34 patients receiving cisplatin-based chemotherapy (20-100 mg/m2), the antiemetic effect of high-dose metoclopramide (HDM) (10 mg/kg iv. loading dose + 7 hours continuous infusion) + lorazepam (L) (2.5 mg x 4 po) was compared with low-dose metoclopramide (LDM) (70 mg) + L (2.5 mg x 2 po) + dehydrobenzperidol (5 mg x 2 im). Among the 29 patients who completed the cross-over, HDM significantly reduced the number of vomiting episodes (p = 0.002) and the degree of nausea (p = 0.004). Seventeen patients preferred the HDM and 4 the LDM regimen (p = 0.01). Sedation was seen in all but 1 patient, and was graded as severe in 6 patients receiving the HDM and in 2 patients receiving the LDM regimen. No extrapyramidal adverse reactions were seen. We conclude that high-dose metoclopramide + lorazepam is a safe antiemetic regimen and significantly superior to low-dose metoclopramide + lorazepam + dehydrobenzperidol. Owing to the severe sedation which occurs in some patients, the dose of lorazepam should be individually adjusted.

The outcome of two different alternating regimens of chemotherapy was investigated in a prospective controlled trial in limited-stage small-cell lung cancer (SCLC). Both regimens comprised cyclophosphamide, lomustine, vincristine, methotrexate, doxorubicin and etoposide administered in different schedules. The investigative regimen (B) included simultaneous administration of cyclophosphamide + lomustine alternating with cyclophosphamide + doxorubicin, and with doxorubicin + lomustine. The hypothetical superiority of this regimen was based on data from experimental animal tumors suggesting potentiated efficacy of the three specific combinations. A total of 234 patients were included, and 113 vs 108 patients were eligible. Median survival in both groups was 48 weeks (p = 0.89). Complete remissions were observed in 36/101 and in 42/99 patients evaluable for response. There was no significant difference in response duration. At restaging after 18 months of chemotherapy 27 patients (16%) and 22 patients (16%), respectively, were free of disease. Six patients, three in each arm, are still alive, 8+ to 10.5+ years after diagnosis. Scheduled doses of the six agents were the same in the two regimens except for a 30% reduction of every second dose of cyclophosphamide in regimen B. Nevertheless, regimen B resulted in significantly more leukopenic patients, septicemic episodes, and blood transfusions, and the dosage of etoposide was more often reduced in arm B than in arm A. The increased toxicity was not associated with improved treatment results.

One hundred thirty-three evaluable patients with advanced breast cancer entered a randomized trial comparing epirubicin 60 mg/m2 with a combination of epirubicin 45 mg/m2 and vindesine 3 mg/m2 day 1 and 8 every 4 weeks. In all 10 premenopausal women an oophorectomy was performed. Seventy-five patients had previously received cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) for advanced disease and 68 had received adjuvant chemotherapy (cyclophosphamide or CMF). Among evaluable patients (72 in the epirubicin group and 61 in the epirubicin + vindesine group) response rates were as follows: complete response--seven versus six; partial response--31 versus 22; no change--16 versus 17 (p greater than 0.40). Median time to disease progression was 6 months in both groups and median survival times were identical (12 months). Thrombocytopenia was less frequent in the epirubicin + vindesine group (p less than 0.01). In the epirubicin + vindesine group, mild to moderate peripheral neuropathy was observed in 40% of the patients. Congestive heart failure developed in one patient with a cumulative dose of epirubicin less than 1000 mg/m2 and in 7 of 15 patients who had greater than 1000 mg/m2. Four died of this cause. In conclusion, epirubicin is effective as a single agent for advanced breast cancer. The combination with vindesine does not increase its efficacy.

The concept of using either alternating or sequential combination chemotherapy with non-cross-resistant combinations was tested in a randomized trial including 301 previously untreated patients with advanced epithelial ovarian carcinoma. The sequential schedule consisted of CAF (cyclophosphamide, doxorubicin, 5-fluorouracil) followed by PH (cisplatin, hexamethylmelamine) in nonresponders, CAF- greater than PH (n = 157), and the alternating regimen consisted of CAF/PH (n = 144). With a median observation time of 54 months, no statistically significant differences were found between the pathologically complete response (PCR) rates of 17% and 16%, respectively, nor were there any statistical differences in median disease-free survival for PCR patients (CAF- greater than PH 34+ months and CAF/PH 26+ months), in overall survival (28 and 24 months, respectively), or in time to treatment failure (10 and 11 months). The overall estimated cure rate was 13%. An equal degree of myelosuppression was seen with the two regimens, whereas neuro- and nephrotoxicity were more pronounced when PH was given sequentially to CAF than with the alternating schedule. We conclude that the sequential and the alternated use of doxorubicin- and platinum-based regimens yield equivalent results and that other approaches should be investigated to improve treatment effects.