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At least 163 records · Page 9Linked to original sources
PubMed1985

Small cell carcinoma of the ovary: a rapidly lethal tumor occurring in the young.

Two patients with metastatic small cell carcinoma of the ovary managed by the Clinical Gynecologic Oncology Service at Roswell Park Memorial Institute are presented. Despite intensive multimodal therapy after extensive cytoreductive surgery, both patients expired from this rare tumor within 6 months of diagnosis. Neither tumor was associated with hypercalcemia, previously reported in the only existing review of the tumor in the world literature. Because of the highly aggressive nature of this cancer, effective combination chemotherapy must be found if the natural history of this tumor is to be altered.

Adolescent↗
PubMed1985

The cyclophosphamide, hexamethylmelamine, 5 fluorouracil (CHF) regimen in the treatment of advanced and recurrent ovarian cancer.

Fifty-one patients with advanced ovarian carcinoma were treated with a combination of cyclophosphamide, hexamethylmelamine, and 5-fluorouracil, CHF. Compared to the hexamethylmelamine, cyclophosphamide, methotrexate, and 5-fluorouracil (Hexa-CAF) regimen, the omission of methotrexate in CHF did not detract from its antitumor activity and it was well tolerated with only mild to moderate toxicity. The CHF combination was as effective as Hexa-CAF and was particularly active in patients who had nonmeasurable/residual disease, classified as less than 2 cm in its greatest diameter at the initiation of chemotherapy. In future studies, CHF should be prospectively compared to other combination using Adriamycin and cis-platinum that with extended use can cause renal and cardiac damage in long-term survivors.

Adult↗
PubMed1985

Recurrent ovarian carcinoma: retreatment utilizing combination chemotherapy including cis-diamminedichloroplatinum in patients previously responding to this agent.

Eleven women with advanced ovarian cancer treated postoperatively with combination chemotherapy (cytoxan, hexamethylmelamine, Adriamycin, and cis-platinum) had disease-free intervals of 5 to 46 months (mean: 22 months) and subsequently developed recurrent carcinoma. Each patient was then retreated with combination chemotherapy which included cis-platinum. There was a 72% response rate to retreatment (36% complete, 36% partial). These overall and complete remission rates are comparable to those of platinum-based combination chemotherapy in patients without prior treatment. Those patients who responded to retreatment had a significantly longer mean survival rate than those who did not.

Adult↗
PubMed1986

Malignant mixed mesodermal tumors of the uterus and ovary treated with cisplatin-based combination chemotherapy.

Twelve patients with malignant mixed mullerian tumors were treated with combination chemotherapy at Vanderbilt University Hospital from 1977 through 1981. Nine patients, all of whom received combination chemotherapy with hexamethylmelamine, cyclophosphamide, doxorubicin, and cisplatin (HCAP), were evaluable for response. Objective responses (all partial responses) were noted in 3 (33.3%) (response rate greater than 10% and less than 55% with 90% confidence limits), a minimal response was noted in one patient, and stable disease in four (50%) patients. Responders survived longer (calculated from the initiation of HCAP) than nonresponders (median 112 vs 19 weeks). These results are not at present statistically different from previous studies utilizing doxorubicin alone, cisplatin alone, the combination of doxorubicin and DTIC, or the combination of vincristine, actinomycin D, and cyclophosphamide.

Aged↗
PubMed1986

CHAP II therapy for epithelial ovarian cancers following primary treatment with platinum-based combination chemotherapy.

Nineteen patients with stage III or IV epithelial ovarian cancer treated on a prospective randomized protocol with either adriamycin and cis-diamminedichloroplatinum or tamoxifen, adriamycin, and cis-diamminedichloroplatinum received a modified "CHAP II" regimen at the time of clinical progression of disease or the finding of occult cancer at second-look surgery. One patient had a clinical complete response lasting 6 months, one had a partial response lasting 23 months, 6 had clinically stable disease for an average of 6.5 months (range 4-15 months), 8 patients had progressive disease, and 3 patients without clinically detectable disease remained disease free for a mean time of 10 months (range 7-16 months). The modified "CHAP II" regimen employed in this study for patients failing prior cis-diamminedichloroplatinum-based regimens appears to have only limited efficacy in inducing objective remissions.

Adult↗
PubMed1986

Hexamethylmelamine, methotrexate, 5-fluorouracil as second line chemotherapy after platinum for epithelial ovarian malignancies.

Thirty-three patients were treated with HexAF after previous treatment with cyclophosphamide (C), Adriamycin (A), and cisplatin (P). The patients had either progressed on CAP, had persistent disease after CAP, or recurred after a negative second look. Treatment schedule was hexamethylmelamine (Hex) 150 mg po qd days 1-14, methotrexate (A) 40 mg/m2 IV days 1 and 8, and 5-fluorouracil (F) 600 mg/m2 IV days 1 and 8. Courses were repeated every 4 weeks. Thirty-one of 33 patients were evaluable for response. Three of 31 patients had partial responses, 7 of 31 had stable disease, and 21 of 31 progressed. Median survival of the responders (n = 3) was 23 months and the nonresponders (n = 28) was 6 months (p = 0.027). Patients with less than 1 cm disease (n = 12) had a median survival of 20 months, and those with greater than 1 cm (n = 21) had a median survival of 6 months (p = 0.004). Toxicity was mild. Even with a statistically significant survival advantage for HexAF responders, we consider a response rate of less than 10% unacceptable.

Adult↗
PubMed1987

Hexamethylmelamine in ovarian cancer after failure of cisplatin-based multiple-agent chemotherapy.

A prospective study was initiated in 1979 to investigate the effect of hexamethylmelamine (HMM) as a second-line chemotherapeutic agent in the treatment of advanced adenocarcinoma of the ovary after failure of cisplatin-based multiple-agent chemotherapy. Of 20 evaluable patients, there were 5 patients (25%) who had objective responses (4 complete and 1 partial). Four additional patients have remained without evidence of disease. Six of these 9 patients are still alive, disease free. There were significant differences (P less than 0.001) in both the progression-free interval and survival time for these 9 patients, 13.3 and 15.1 months, respectively, as compared to the 15 nonresponders, 0.8 and 5.8 months, respectively. There was no significant difference in survival between the 4 patients with stable disease and the 11 patients with progressive disease. Performance status less than 2 (P less than 0.05) and absence of clinically measurable disease at the time of entry into the study (P less than 0.05) were found to be significant variables with regard to determining outcome. Only 2 of 24 patients suffered severe enough side effects from the HMM to warrant its discontinuation. This study demonstrates that HMM at doses of 6-8 mg/kg/day for 21 out of every 28 days can induce a complete response and provide an extended disease-free interval and prolonged survival with tolerable side effects in a significant number of patients with ovarian cancer who have previously failed cisplatin-based multiple-agent chemotherapy.

Adenocarcinoma↗
PubMed1988

The treatment of advanced ovarian carcinoma (I): clinical variables associated with prognosis.

New therapy regimens including cytoreductive surgery and cisplatin-based combination chemotherapy have improved survival for a small group of patients with advanced ovarian carcinoma. However, for the entire group survival remains poor. In this analysis of 65 patients treated at Leiden University Medical Center, the patient group that benefited the most from this approach was characterized by a younger age, good performance status, less extensive disease, low histologic grade and the absence of peritoneal carcinomatosis and ascites, and residual disease less than or equal to 15 mm (successful cytoreduction) after the first operation. Patients who did not have these favorable characteristics but in whom the first operation resulted in residual disease less than or equal to 15 mm, did survive worse than the other patients with individual tumor nodules less than or equal to 15 mm, but still better than those in whom a successful cytoreduction at the first operation could not be achieved. The diameter of the largest residual disease, the diameter of the largest metastasis before cytoreduction, and the presence of ascites and peritoneal carcinomatosis influenced prognosis. Thus the initial tumor burden as well as the burdened tumor volume left behind are of significance with respect to prognosis. However, in the Cox regression analysis the performance status and ascites proved to be the only independent factors influencing survival. A prospective study is needed to establish the proper value of cytoreductive surgery in advanced ovarian carcinoma.

Altretamine↗
PubMed1988

Advanced carcinoma of the ovary with central nervous system relapse.

Interdisciplinary protocols for management of advanced adenocarcinoma of the ovary have resulted in prolonged patient survival. A subset of patients is emerging in whom central nervous system (CNS) relapse occurs even following negative second-look procedures (SLP). Seven of 342 eligible patients entered in a National Cancer Institute of Canada Trial for Ovarian Cancer, from February 1, 1980 to March 31, 1984, had CNS relapse. All patients received adriamycin and cisplatin. SLP was performed in 5 patients, 3 of whom were complete responders (CR). Two additional patients failed to complete their chemotherapy and had progressive pelvic disease. The median age of these 7 patients was 57 years, their overall survival time was 28 months, compared with an average age of 58 years and survival of 21.6 months, for the entire group. Two patients had prolonged survival after their CNS relapse; 1 patient lived 26 months, and the other, who underwent craniotomy for primary management of the metastasis survived 18 months. Confirmation of metastatic disease was obtained in 4 of the 7 patients. The results of this study suggest that management of CNS involvement in adenocarcinoma of the ovary should be determined by overall performance status even in the presence of generalized disease.

Adenocarcinoma↗
PubMed1989

Phase II evaluation of peroral carmofur, cyclophosphamide, and hexamethylmelamine as a second-line therapy in advanced epithelial ovarian carcinoma.

A prospective phase II study was performed to evaluate the effect and tolerability of a peroral combination chemotherapy consisting of hexamethylmelamine, cyclophosphamide, and carmofur in patients with epithelial ovarian cancer previously heavily treated by cisplatin-based chemotherapy but no longer responding to it. Of the 27 patients 1 showed a clinical complete remission lasting 15+ months and 4 a partial remission of 6+ to 21 months. A further 7 patients had an unchanged situation of 4 to 13+ months. The median survival of the nonresponders was 3 months. The side effects were tolerable, mostly nausea and vomiting. Only 4 of 27 patients suffered from severe vomiting causing discontinuation of the therapy. The peroral ambulatory chemotherapy prolonged markedly the overall survival of about one-half of the patients with ovarian cancer who previously failed to respond to cisplatin-based chemotherapy.

Administration, Oral↗
PubMed1989

Concurrent chemotherapy and single high-dose plus whole abdominopelvic radiation for persistent ovarian carcinoma.

Twenty-two patients were treated with concurrent single high-dose and standard fractionated abdominopelvic radiation and chemotherapy (cisplatin or hexamethylmelamine). Those who had prior cisplatin received hexamethylmelamine and radiation (16 patients) while those without prior cisplatin received cisplatin and radiation (6 patients). The primary aim of the study was to assess the tolerance and effectiveness of concurrent radiation and chemotherapy in patients who had failed prior chemotherapy. All patients experienced mild to moderate nausea, vomiting, and diarrhea. Hematologic adverse effects were minimal. Three patients requiring laparotomy for radiation induced small bowel obstruction had confirmed complete responses but 2 died acutely of treatment-related complications without evidence of tumor. In the 15 patients with suboptimal disease (greater than 1 cm residual disease) prior to the study, only 1 had a complete response while 2 of 7 optimal patients (less than or equal to 1 cm residual disease) had a complete response. All 3 complete responders received cisplatin and 2 had 1 cm or less of residual disease prior to the study. In the hexamethylmelamine group 3 of 16 patients had a partial response. Concurrent single high-dose whole abdominopelvic radiation and cisplatin may be effective in patients with minimal disease (less than or equal to 1 cm); however, radiation-associated bowel complications were severe.

Abdomen↗
PubMed1990

Hexamethylmelamine as a single second-line agent in ovarian cancer.

Fifty-two patients with advanced ovarian cancer were treated with single-agent hexamethylmelamine (HMM), 260 mg/m2 po per day for 14 days followed by 14 days off drug. All patients had been previously treated with chemotherapy. Of these patients, 92% (48/52) received cisplatin and cyclophosphamide +/- doxorubicin prior to hexamethylmelamine. Two additional patients received other cisplatin-based regimens. Fifteen percent (8/52) were found to have no evidence of disease (NED) at the completion of treatment with HMM. Five of these patients are alive at 12 to 65 months (median follow-up of 32 months); one patient died at 41 months of an intercurrent illness with no clinical evidence of recurrence; two patients died of recurrent tumor at 21 and 31 months. The median survival of the series of 52 patients is 11 months: 9 months for patients who did not respond versus 41 months for patients with NED post-HMM (P less than 0.05). The regimen was well tolerated: moderate gastrointestinal toxicity was reported by 8 patients; only one patient reported severe gastrointestinal toxicity. Moderate neurologic toxicity (primarily sensory) was reported by 5 patients, 3 patients experienced white counts less than 2000 or platelet counts less than 100,000, and no patient sustained severe hematologic toxicity. This moderate-dose intermittent regimen was associated with moderate toxicity and was well accepted by patients. The overall response is comparable to or higher than that reported for more toxic chemotherapy regimes. Based on these data and those recently reported by other authors, hexamethylmelamine should be considered in the treatment of recurrent ovarian cancer.

Adult↗
PubMed1992

Hexamethylmelamine as second-line therapy in platin-resistant ovarian cancer.

A total of 61 patients with recurrent or persistent clinically measurable platin-resistant epithelial ovarian carcinoma were treated with 260 mg/m2 oral hexamethylmelamine daily for 14 days, repeated at 4-week intervals. Platin resistance was defined as progression or stable disease during cis- or carboplatin treatment (used alone or in combination with other drugs), or relapse within 6 months after the end of that therapy. Fifty patients were evaluable for response and 57 for toxicity. The objective response rate was 14% (3 complete and 4 partial responses). The response rate was higher in patients with relapse within 6 months than in patients with progression or stable disease on platin-based therapy. This observation underscores the importance of defining response and time to progression after first-line chemotherapy. The median duration of response was 8 months and the median survival in responding patients was 9+ months versus 5 months for patients with progression on hexamethylmelamine. Nausea and vomiting requiring antiemetic treatment occurred in 8 (14%) patients and reversible peripheral neuropathy in 3 patients. Two patients developed agitation, insomnia, and depression during hexamethylmelamine therapy. In conclusion, the 14% objective response rate and the occurrence of complete responses with oral hexamethylmelamine treatment in a group of ovarian cancer patients with true platin resistance are noteworthy.

Adult↗
PubMed1985

Weak mutagenicity to Salmonella of the formaldehyde-releasing anti-tumour agent hexamethylmelamine.

Hexamethylmelamine (HEMLA) is a metabolism-dependent formaldehyde-releasing agent related in structure to hexamethylphosphoramide (HMPA). Both compounds are known to be mutagenic to Drosophila. HMPA, in common with the other formaldehyde-releasing agents studied, is non-mutagenic to Salmonella. The present paper describes the mutagenicity of HEMLA to strain TA100 of Salmonella typhimurium. Activity is dependent upon both the use of a pre-incubation assay protocol and on high concentrations of Aroclor-induced rat liver in the S9 mix. HMPA was inactive under similar conditions of test.

Altretamine↗
PubMed1982

cis-Dichlorodiammineplatinum (II) and hexamethylmelamine in advanced ovarian carcinoma: a phase II study.

Thirty-eight previously treated patients with ovarian carcinoma received a combination of cis-dichlorodiammineplatinum (II) (CDDP) and hexamethylmelamine (HMM). The schedule was CDDP 75 mg/m2 i.v. with forced diuresis on day 1, followed by HMM 200 mg/m2 p.o. on days 8-21, repeated every 4 weeks. In 29 evaluable patients an overall response rate (CR + PR) of 35% with a median response duration of 4.5 months was observed. The performance status seemed to be an important prognostic factor. The gastrointestinal- and neurotoxicities were severe and resulted in dose modification and/or drug discontinuation in half of the patients. In conclusion, CDDP and HMM is an active drug combination in advanced ovarian carcinoma resistant to conventional chemotherapy. A possible superiority of this combination compared with CDDP or HMM alone has to await randomized trials.

Adult↗
PubMed1984

The chemosensitivity of a new experimental model--the M5076 reticulum cell sarcoma.

The M5076 reticulum cell sarcoma is a murine tumour of potential value in experimental chemotherapy. Experiments were conducted to ascertain the growth characteristics and chemosensitivity of this neoplasm in the BDF1 mouse. The intramuscular tumour proved to be responsive to the alkylating agents, nitrosoureas, procarbazine, DTIC and treosulphan, yet insensitive to the antimetabolites and only weakly responsive to adriamycin. Analogues of the antitumour agents hexamethylmelamine and N-methylformamide were tested against this neoplasm. The patterns of activity determined for these analogues against this tumour were identical to those previously reported against other model systems.

Altretamine↗