melphalan and Cystadenocarcinoma

Poor survival rates of ovarian carcinoma have continued to be a cause of grave concern over decades and led to growing attention and alert in recent years. Promising results have already been recorded. More knowledge of important factors with relevance to prognosis has been helpful in unitising large-scale therapeutic studies for better comparability, a desire which had been unfulfilled in the past. Close interdisciplinary cooperation between gynaecologists, radiotherapists, and chemotherapists proved to be essential to optimum programmes of therapy. Persistent basic research for better understanding of biological behaviours of ovarian carcinomas and of so far unknown factors of prognosis and persistent efforts for earlier diagnosis of ovarian carcinoma are just as important. This is the only way to more effective control of the disease which still is, diagnostically and therapeutically, one of the major problems in gynaecology.

Topics: Carcinoma; Chlorambucil; Cyclophosphamide; Cystadenocarcinoma; Female; Humans; Melphalan; Mesonephroma; Neoplasm Staging; Ovarian Neoplasms; Prognosis; Thiotepa

Forty-six patients with recurrent ovarian cancer were reoperated, and cancer samples for the subrenal capsule assay (SRCA) were collected from 23 of them, whereas this test was not done in the remaining 23 control patients. The SRCA was evaluable in 22 cases (96%). Taken together, no significant difference appeared in the 3 years' survival figures between the groups: seven of 22 patients (32%) with the evaluable SRCA and six of 23 control patients (26%) were alive. However, a further analysis of the data revealed that the SRCA guided the selection of chemotherapy only in 15 patients, whereas tumour samples were resistant to all cytostatics tested in six cases and toxic side-effects limited the clinical application of the test results in the remaining one case. Four of the 11 patients (36%) whose further chemotherapy was strictly chosen based on the SRCA and seven of the 24 patients (29%) whose treatment was based on physician's choice survived at least 3 years. Our conclusion is that the SRCA is of limited value in the selection of second-line chemotherapy in recurrent ovarian cancer.

Topics: Adult; Aged; Altretamine; Animals; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cyclophosphamide; Cystadenocarcinoma; Doxorubicin; Drug Screening Assays, Antitumor; Epirubicin; Female; Follow-Up Studies; Humans; Melphalan; Mice; Middle Aged; Ovarian Neoplasms; Subrenal Capsule Assay

In October 1978, the Swedish Cooperative Ovarian Cancer Study Group started a randomized comparison of doxorubicin 40 mg/m2 and melphalan 0.4 mg/kg with melphalan 1 mg/kg every four weeks in International Federation of Gynecology and Obstetrics (FIGO) stages III and IV ovarian cancer of serous and anaplastic histology. One hundred sixty-eight patients entered the study, and 148 were evaluable at five years or longer. All had residual tumors larger than 10 cm, with appropriate stratification according to stage, histologic grade, and age. Definition of response was according to World Health Organization (WHO) criteria except that we required three months' regression of all clinically detectable tumors instead of one month. Seventy-three women treated with doxorubicin plus melphalan had a significantly higher response rate than 75 patients treated with melphalan alone (54.7 versus 26.7%; P less than .0001), median duration of response (13.0 versus 7.3 months; P less than .0057), and median survival time (18.5 versus 10.5 months; P less than .0001). Combined treatment produced significantly more complete remissions than single-agent therapy (30 versus 6.7%; P less than .001). At 60 months, ten patients were alive in the doxorubicin plus melphalan group, compared with three in the melphalan group. Temporary bone marrow depression was significantly more frequent in the melphalan-treated patients, but subjective side effects were the same in both groups.

Topics: Actuarial Analysis; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Cystadenocarcinoma; Doxorubicin; Female; Humans; Melphalan; Middle Aged; Ovarian Neoplasms; Random Allocation; Sweden; Time Factors

Twenty-four fully staged, previously untreated patients with advanced ovarian carcinoma were prospectively randomized to either intensive intravenous cyclophosphamide or conventional oral Melphalan therapy. The median durations of initial remissions (5 and 6 mo) and the median durations of survival (15 and 14 mo) were similar for the two regimens but the toxicity of the intensive regimen was excessive. Followup indicates that long term disease free survivals are possible in those patients who achieve complete remissions on chemotherapy alone as three of the four patients achieving complete remission in the present study remain free of disease with a median survival in excess of 30 mo. High dose intensive alkylating agent therapy in the manner used in the present study fails to enhance the response to chemotherapy and produces unacceptable toxicity.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Administration, Oral; Cyclophosphamide; Cystadenocarcinoma; Dose-Response Relationship, Drug; Female; Humans; Injections, Intravenous; Laparoscopy; Melphalan; Ovarian Neoplasms; Remission, Spontaneous; United States

The importance of dose intensity has been suggested in ovarian carcinoma. We retrospectively evaluated the long-term results of melphalan-based high-dose chemotherapy (HDC) with hematopoietic rescue in a unicentric series of 33 patients with advanced ovarian cancer sensitive to first-line chemotherapy. Before HDC, treatment with debulking surgery and platinum-based chemotherapy was followed by second-look operation (SLO). HDC consisted of melphalan (n = 8), melphalan and cyclophosphamide (n = 9), or melphalan, etoposide and carboplatinum (n = 16). Toxicity was mainly hematological. One death occurred from infection during aplasia. With a median follow-up of 60 months after intensification, the 5-year progression-free survival (PFS) rate was 29% and the 5-year overall survival (OS) rate was 45%. Survival differed significantly according to tumor status at SLO. Women with microscopic or macroscopic disease at SLO, ie with a pathological partial response to first-line therapy (PPR), had survivals of 7% at 5 years, similar to other salvage therapies. Better results were obtained in the 20 women with a complete pathological response (PCR) at SLO with 43% 5-year PFS (median, 51 months) and 75% 5-year OS (median not reached). In conclusion, melphalan-based HDC with hematopoietic rescue had an acceptable toxicity in patients with chemosensitive advanced ovarian cancer. In situations of salvage therapy for patients in PPR, this treatment was not effective in long-term analysis. On the contrary, long-term results were favorable in patients with PCR, suggesting further prospective randomized studies comparing HDC and other consolidation treatments should be undertaken in this particular situation.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Cyclophosphamide; Cystadenocarcinoma; Disease-Free Survival; Etoposide; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Humans; Laparotomy; Melphalan; Middle Aged; Neoplasm Staging; Ovarian Neoplasms; Reoperation; Retrospective Studies; Survival Rate; Time Factors; Transplantation, Autologous

We initiated in February 1982 a pilot study of high dose melphalan (HDM) and ABMT as consolidation treatment for ovarian carcinoma. Eleven patients entered into this study; 6 patients received HDM and ABMT (group 1), 5 patients received HDM in combination with flash abdominal radiotherapy followed by ABMT (group 2). Two of 6 group 1 patients and 3 of 5 group 2 patients are still alive with NED more than 3 years after ABMT (58+, 72+, 37+, 39+, 43+) and are hopefully cured. Main toxicity was haematological, we have not observed any death related to therapy. HDM and ABMT compared favorably with other consolidation treatments (abdominopelvic radiotherapy or IP chemotherapy) and merits a larger evaluation.

Topics: Abdominal Neoplasms; Adult; Bone Marrow Diseases; Bone Marrow Transplantation; Combined Modality Therapy; Cystadenocarcinoma; Female; Humans; Melphalan; Middle Aged; Ovarian Neoplasms; Ovariectomy; Prognosis; Remission Induction; Transplantation, Autologous

A multidrug resistance phenotype is frequently observed in animal and human cell lines selected for in vitro resistance to a single chemotherapeutic agent. Overexpression of a highly conserved cell-surface glycoprotein (P-glycoprotein) is consistently associated with this phenotype in these mutant lines. A monoclonal antibody against P-glycoprotein was used to examine tumor samples from five patients with advanced ovarian cancer for evidence of P-glycoprotein overexpression. High levels of P-glycoprotein were detected in samples from two patients suggesting that a multidrug resistance mutation may also occur in ovarian cancer. This finding has broad implications for the understanding of nonresponse to chemotherapy in a variety of human neoplasms, and may provide a rational explanation for failure of chemotherapy in treatment of advanced ovarian cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cisplatin; Cyclophosphamide; Cystadenocarcinoma; Doxorubicin; Drug Resistance; Female; Genetic Markers; Glycoproteins; Humans; Melphalan; Middle Aged; Ovarian Neoplasms; Phenotype

The results of chemotherapy (frequency and duration of remission) of 237 cases of primary and 119-recurrent serous cystadenocarcinoma of ovaries are discussed.

Topics: Antineoplastic Agents; Combined Modality Therapy; Cyclophosphamide; Cystadenocarcinoma; Female; Humans; Melphalan; Neoplasm Recurrence, Local; Ovarian Neoplasms; Prognosis; Thiotepa; Time Factors; Triazines

Variables associated with a negative second-look laparotomy in patients with stage III epithelial ovarian carcinoma are analyzed. Fifty-six patients were clinically free of disease after systemic chemotherapy and were subjected to second-look laparotomy to assess tumor status. Eighteen of these patients (32.1%) had no evidence of malignancy. Eight (14.3%) additional patients with no gross evidence of disease at laparotomy had microscopic persistence; five of these had disease documented in the pelvic or para-aortic lymph nodes. Significant variables associated with a histologically and cytologically negative second-look operation were low tumor grade (P less than .01), the use of cis-platinum containing combination chemotherapy (P less than .01), patient age less than or equal to 50 years (P less than .02), small residual tumor (less than 0.5 cm) before chemotherapy (P less than .05), and metastatic tumor less than or equal to 10 cm before initial cytoreduction (P less than .05). Patients treated with six to nine cycles of combination chemotherapy had the same probability of a negative second-look laparotomy as those treated with ten to 12 cycles. Multivariate discriminate analysis indicated that patients with low tumor grade, those receiving cis-platinum containing combination chemotherapy, and those with minimal residual tumors (less than 0.5 cm) after primary cytoreductive surgery correctly classify second-look status in 78.6% of patients. Until a nonsurgical method of monitoring subclinical disease is available, a through second-look laparotomy, including a pelvic and para-aortic lymphadenectomy, should be performed.

Topics: Adult; Aged; Analysis of Variance; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cystadenocarcinoma; Female; Follow-Up Studies; Humans; Laparotomy; Lymph Node Excision; Lymphatic Metastasis; Melphalan; Middle Aged; Neoplasm Staging; Ovarian Neoplasms; Reoperation

Acute nonlymphocytic leukemia developed in a 57-year-old woman following adjuvant therapy with melphalan for ovarian carcinoma. Maturation of differentiating marrow myeloid and erythroid precursors was megaloblastic. The serum vitamin B12 level was low, and Schilling test revealed vitamin B12 malabsorption correctable with intrinsic factor. Megaloblastic maturation of the marrow cells was converted to normoblastic following treatment with vitamin B12 and folic acid. However, blast cells persisted in the marrow, and cytogenetic analysis revealed aneuploidy and trisomy 18. In contrast to the marrow blast cells, there was a decline in circulating blast cells following vitamin replacement, suggesting that these cells were capable of maturation but required vitamin B12 for this purpose.

Topics: Acute Disease; Anemia, Pernicious; Bone Marrow; Cell Division; Cystadenocarcinoma; Female; Folic Acid; Hemoglobins; Humans; Leukemia; Melphalan; Middle Aged; Ovarian Neoplasms; Vitamin B 12; Vitamin B 12 Deficiency

The paper presents the results of intratumoral chemotherapy of 32 cases of single metastases of stage III-IV ovarian cancer into the Douglas pouch. The metastases were detected at different stages after primary treatment. Thiotepa, cyclophosphamide, sarcolysin and methotrexate were administered in 81.2, 9.4, 6.2 and 3.1% of cases, respectively. A clinically-significant effect was recorded in 14 out of 32 cases (43.7%); tumor process was arrested in 15 cases (46.9%); treatment failed in 3 cases (9.4%). Toxic side-effects were less frequent and pronounced than in patients given standard systemic monochemotherapy.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Aged; Antineoplastic Agents; Cyclophosphamide; Cystadenocarcinoma; Douglas' Pouch; Endometriosis; Female; Humans; Melphalan; Methotrexate; Middle Aged; Ovarian Neoplasms; Peritoneal Neoplasms; Thiotepa

The data on 41 patients with epithelial malignant tumors of the ovaries, who received sarcolysin at different stages of combined treatment, were analyzed. The following factors of therapeutic effect of sarcolysin were established: age of 41-50 years, presence of ascites, administration by two routes--intravenously and intracavitarily and a total dose in excess of 160 mg. Still another factor is contributed by the extent of surgical procedure carried out as primary treatment.

Topics: Adenocarcinoma; Adult; Cystadenocarcinoma; Endometriosis; Female; Humans; Melphalan; Middle Aged; Ovarian Neoplasms

Topics: Castration; Child; Cystadenocarcinoma; Female; Humans; Melphalan; Ovarian Neoplasms

A 67-year-old woman suffered from an ovarian carcinoma with lymph nodes metastasis. During 3 years, she was treated with alkylating agents (Melphalan). At the end of therapy, no recurrence was observed. Two years later, she developed concomitantly pyoderma gangrenosum and acute myelomonocytic leukaemia. Death occurred rapidly. The association between pyoderma gangrenosum and acute leukaemia is discussed in the light of 16 cases previously reported in the literature. In this case, an induction of leukaemia by cytostatic drugs seems likely. The authors conclude that pyoderma gangrenosum may be considered as a cutaneous signs of acute leukaemia.

Topics: Aged; Cystadenocarcinoma; Female; Humans; Leukemia, Myeloid, Acute; Lymphatic Metastasis; Melphalan; Ovarian Neoplasms; Pyoderma

Fibrinogen/fibrin degradation products (FDP) in the serum of 50 patients with ovarian carcinoma was examined by Nyléhn's immunochemical method. FDP were rarely found in early but frequently in advanced stages of ovarian tumours. With successful treatment, FDP decreased; otherwise persistently high FDP concentrations were observed in the serum. The determination serum FDP might be a valuable aid in assessing the effect of treatment.

Topics: Adult; Aged; Carcinoma; Cyclophosphamide; Cystadenocarcinoma; Female; Fibrin Fibrinogen Degradation Products; Fluorescent Antibody Technique; Humans; Melphalan; Middle Aged; Ovarian Neoplasms

We report the serum levels of carcinoembryonic antigen (CEA) in 109 patients with ovarian cancer. Histology, degree of differentiation, and clinical stage influenced the incidence of positive CEA. Although CEA was significantly raised in patients with a variety of tumours, the highest incidence (77 per cent) was found in those with serious cystadenocarcinoma. Nearly all (94 per cent) of the poorly differentiated tumours were associated with a positive CEA result. Serial CEA levels provided a useful guide to management during cytotoxic chemotherapy, rapidly falling levels indicating a favourable tumour response which was reflected clinically. However, only two-thirds of tumours were associated with detectable CEA levels in serum, day-to-day variations in individual serum levels occurred, and CEA levels tended to fall paradoxically during terminal illness. The significance of persistently low levels in the apparent absence of disease was uncertain.

Topics: Adenocarcinoma; Carcinoembryonic Antigen; Cystadenocarcinoma; Cystadenoma; Dysgerminoma; Endometriosis; Female; Follow-Up Studies; Granulosa Cell Tumor; Humans; Melphalan; Mesonephroma; Ovarian Neoplasms; Pregnancy

Topics: Antibody Formation; Antineoplastic Agents; Body Weight; Cyclophosphamide; Cystadenocarcinoma; Endometriosis; Erythrocyte Count; Female; Humans; Leukocyte Count; Melphalan; Mesonephroma; Middle Aged; Ovarian Neoplasms; Time Factors

Topics: Adenocarcinoma, Mucinous; Cyclophosphamide; Cystadenocarcinoma; Dactinomycin; Drug Combinations; Female; Fluorouracil; Humans; Melphalan; Neoplasm Metastasis; Ovarian Neoplasms

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Ascites; Chlorambucil; Cobalt Isotopes; Cyclophosphamide; Cystadenocarcinoma; Dactinomycin; Endometriosis; Female; Fluorouracil; Humans; Melphalan; Ovarian Neoplasms; Radiotherapy, High-Energy; Thiotepa; Vinblastine; Vincristine

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Antineoplastic Agents; Cyclophosphamide; Cystadenocarcinoma; Dactinomycin; Female; Fluorouracil; Humans; Melphalan; Ovarian Neoplasms

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Cyclophosphamide; Cystadenocarcinoma; Dactinomycin; Female; Fluorouracil; Humans; Mechlorethamine; Melphalan; Ovarian Neoplasms; Thiotepa; Vinblastine

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Antineoplastic Agents; Carcinoma; Cystadenocarcinoma; Cystadenoma; Endometriosis; Female; Humans; Melphalan; Middle Aged; Ovarian Neoplasms