Successful chemotherapy for disseminated testicular Sertoli cell tumour.
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Abdominal Neoplasms↗
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Medical Research Council study on chemotherapy in advanced ovarian cancer. Medical Research Council's Working Party on ovarian cancer.
A total of 264 eligible patients with advanced ovarian cancer were randomised to single or triple agent cytotoxic therapy; 261 were available for analysis. The treatments were continuous oral cyclophosphamide (arm S), and a combination of oral cyclophosphamide, hexamethylmelamine and methotrexate on a pulsed basis (arm T). Mortality attributed to cancer was slightly lower on arm T (p = 0.06), but this was offset by the greater toxicity of this regimen, and overall survival and activity index were similar on the two arms. There was thus little evidence of greater clinical benefit on the triple agent regimen. Tumour mass removed at operation, extent of remaining tumour and age all showed significant correlation with prognosis. Survival was longer in patients whose disease responded to either therapeutic regimen.
Aged↗
Computed tomography prior to surgery for ovarian carcinoma.
The value of investigation of patients with ovarian carcinoma by preoperative computed tomography scan was evaluated in all the patients operated on during the last 2 years; 22 patients were included in this study and evaluated. In 11 patients the scan was performed prior to the primary surgery and in the other 11 patients before second look following chemotherapy. CT scan was found to be highly sensitive in detecting ascites, pelvic wall extension and spread or involvement of the uterus. Peritoneal and omental spread was detected in only half of the patients before primary surgery. Prior to second look operation CT scan was effective in excluding liver metastasis, ascites, paraaortic lymph node enlargement, pelvic wall extension and pelvic residual tumour. Generally, CT scan failed to detect peritoneal and omental spread. It is an important tool for preoperative evaluation of the extension of the disease and planning of surgery, but still, the final staging deserves explorative laparotomy.
Altretamine↗
Role of chemotherapy in the future treatment of ovarian cancer.
Platinum-based chemotherapy has led to an improvement in complete response rates and duration of median remission, but has only given a modest improvement in overall survival in patients with advanced ovarian cancer. Chemotherapy will in the future focus upon: (1) improving the complete remission rate with new induction regimens; (2) identifying strategies capable of converting partial remission into complete remission; (3) preventing or delaying recurrences in patients who do achieve a complete remission; (4) identifying mechanisms of antineoplastic drug resistance and pharmacologic techniques capable of reversing drug resistance. Among the treatment approaches being utilized are high-dose chemotherapy with autologous bone marrow transplantation, development of new chemotherapeutic regimens which include Taxol and hexamethylmelamine, and intraperitoneal chemotherapy. In addition, our understanding of the mechanisms of antineoplastic drug resistance has led to the development of novel therapeutic approaches. It has been demonstrated that resistance to platinum and alkylating agents is associated with both increased concentrations of cellular glutathione (GSH) as well as an increased capacity of tumor cells to repair damage to DNA. Inhibition of GSH biosynthesis with buthionine sulfoximine (BSO), a synthetic inhibitor of the enzyme gamma glutamyl cysteine synthetase, has led to the potentiation of alkylating agent activity in vitro and in vivo. A phase I trial of BSO plus melphalan is currently in progress and a trial of BSO plus carboplatin is planned. Inhibition of the DNA repair process with aphidicolin potentiates the cytotoxicity of cisplatin in drug-resistant tumor cells. Clinical trials of aphidicolin plus cisplatin await the completion of ongoing phase I trials of aphidicolin.
Alkaloids↗
Absorption and metabolism of hexamethylmelamine and pentamethylmelamine in rat everted perfused gut segments: correlation with in-vivo data.
The intestinal oxidative metabolism of hexamethylmelamine (HMM) and pentamethylmelamine (PMM) has been studied in microsomes, isolated mucosal cells and intestinal perfused segments. (sub) Cellular systems revealed an almost equal Km (53-65 microM) and Vmax (5.6-7.0 nmol min-1 g-1 intestine) for both compounds. Detailed studies in everted intestinal perfused segments, showed that HMM is metabolized to a far greater extent than PMM (e.g. 11-times, at 80 microM substrate concentration) while PMM transport was 3 times greater than the transport of unchanged HMM. Only when perfused segments were used as an in-vitro tool was a good correlation observed between the in-vivo and in-vitro rate of intestinal metabolism of HMM and PMM. It is concluded that this is due to preservation of structural integrity of the mucosa for both absorptive and metabolic processes.
Altretamine↗
Anticancer chemotherapy.
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Alkylating Agents↗
Recurrent ovarian cancer: how important is it to treat to disease progression?
Ovarian cancer is increasingly recognized as a chronic disease whose treatment is often characterized by administration of multiple, sequential active agents, each of which may or may not be accompanied by a tumor response. Despite the large proportion of patients who relapse and undergo longer-term treatment, the question of optimal treatment duration has not been fully addressed to date. For patients who progress on therapy, the answer is straightforward: they are switched to another active agent, presumably having a different mechanism of action from previous therapies with, ideally, limited overlapping toxicities. However, for patients who remain in partial response or who have stable disease, the answer is less apparent and less clear. The majority of oncologists believe that treatment beyond 6 cycles of a given therapy does not provide any additional benefit to patients. There are some data to support that treatment strategy. However, with the advent of new, less toxic agents, treatment to progression should be further explored. Agents that are potentially well suited for extended treatment intervals may include such properties as absence of cumulative toxicity, non-cross-resistance, positive benefit on quality of life, and convenient schedule. A number of active agents in ovarian cancer (platinum, paclitaxel, topotecan, liposomal doxorubicin, docetaxel, gemcitabine, and etoposide) will be reviewed in the context of what is known about cumulative toxicity, potential adverse effects on patients' quality of life, and evidence addressing the potential benefits of longer-term treatment.
Altretamine↗
[Chemotherapy of advanced epithelial ovarian carcinoma].
The role of chemotherapy in the management of carcinoma of the ovary is becoming increasingly important. It is the first-line treatment of choice in all patients with stage III or IV of disease and where tumor deposits larger than 2 cm remain in the abdominal cavity after surgery. Until recently the main drugs have been used to treat ovarian cancer are the alkylating agents. In addition to these agents three new active drugs - hexamethylmelamine, adriamycin, cis-platinum - have been studied and their potential role is more carefully defined. Today the definition and better understanding of prognostic criteria play a primary role in the selection of treatment drugs. With continued efforts to define optimum treatment modalities and by application of some of the new treatment ideas coming from the laboratory, perhaps the poor survival of patients with ovarian epithelial malignancies will be further improved.
Alkylating Agents↗
The treatment of ovarian cancer by a multimodality approach: remission induction with chemotherapy--hexa PAMP and PAMP regimens--followed by whole-abdominal radiation.
Seventy-six evaluable patients with ovarian carcinoma stages FIGO IIb, IIc, III, and IV, either received cis-platin (P) (80 mg/m2 iv. day 1), melphalan (PAM) (12 mg/m2 i.v. day 2) and hexamethylmelamine (HEXAPAMP) (135 mg/m2 orally days 8 to 21) or the same dose of cis-platin and melphalan but no hexamethylmelamine (PAMP) every four weeks. In 24 patients (32%) a surgically ascertained CR was achieved. 16 of these received follow-up radiation treatment to the whole abdomen. At present 19 patients are without relapse (average time 24 months). The trial has not been concluded. Particularly no predictions can be made on the value of follow-up radiation therapy in obtaining long-term remission rates.
Adult↗
A phase III study in lung carcinoma comparing hexamethyl-melamine (NSC 13875) to dibromodulcitol (NSC 104800) 1,2.
A phase III study was designed comparing the effectiveness of Hexamethyl-melamine (NSC 13875) to Dibromodulcitol (NSC 104800) in lung carcinoma. 250 of the 316 patients entered on the study were stratified into groups according to stage of disease and cell type. The results showsed Hexamethylmelamine to be more effective in patients with squamous cell carcinoma and slightly superior to Dibromodulcitol in patients with anaplastic/undifferentiated cell carcinoma, whereas Dibromodulcitol proved to be more effective in patients with adenocarcinoma.
Adenocarcinoma↗
Combination chemotherapy with CCNU (NSC-79037),hexamethylmelamine (NSC-13875) and methotrexate (NSC-740) in advanced bronchogenic carcinoma.
18 patients with metastatic or recurrent bronchogenic carcinoma and one patient with a squamous cell carcinoma of the trachea were treated with a combination of CCNU, hexamethylmelamine and methotrexate. Objective remissions were observed in 3/19 (16%): 1 complete, 1 partial (greater than 50%) and 1 incomplete (less than 50%). However, the patient with the complete response was the only drug death, on day 21. Remission duration in the other two patients was 3 and 9+ months respectively. One patient with oat cell carcinoma experienced no tumor progression for 5 months. This combination resulted in severe gastrointestinal toxicity in 5/19, severe thrombopenia in 12/19 and severe neutropenia in 6/19. We conclude that the combination as used here resulted in no increased clinical effectiveness and proved to be quite toxic.
Aged↗
Therapy of small cell carcinoma of the lung with hexamethylmelamine.
Hexamethylmelamine (HXM) is one of the substituted melamines derived from cyanuric chloride [1]. Previous studies with HXM have shown activity against small cell carcinoma of the lung, when it was given as a single agent [2, 3]. Because of relatively mild bone marrow toxicity, HXM was subsequently given in combination with other drugs and/or radiation therapy, in order to improve the therapeutic results. In this paper, our experience with HXM in treatment of small cell carcinoma of the lung is summarised.
Adult↗
Treatment of ovarian cancer with a combination of cis-platinum, adriamycin, cyclophosphamide and hexamethylmelamine.
During the last 2 1/2 years, 38 patients with ovarian cancer were treated with a combination of cisplatinum (CPDD), 50 mg/m2, adriamycin, 30 mg/m2, cyclophosphamide, 300 mg/m2, on day 1; and hexamethylmelamine (HMM), 6 mg/kg daily, for 14 days. Each course was repeated monthly. 2 patients had stage II, 14 stage III and 22 stage IV disease. 14 of the 38 patients were previously treated with chemotherapy, 1 with radiation, 6 with both chemotherapy and radiation, and 17 did not have any treatment before CPDD combination. 31 of the 38 cases (81.5%) demonstrated objective responses lasting for 2 months or more. These responses were partial in 19 and complete in 12 cases. Hematologic toxicity was moderate and with reversible anemia developing in 71% of patients. Gastrointestinal side effects from CPDD were universal. HMM gastrointestinal toxicity necessitated discontinuation of the drug in 5 patients. Severe nephrotoxicity was observed in 2 patients but was reversible. There were no drug-related deaths.
Acute Kidney Injury↗
Phase II trial of combination chemotherapy of colonic cancer with 5-fluorouracil, mitomycin C, and hexamethylmelamine.
HexMF consists of hexamethylmelamine 150 mg/m2 D2-15, mitomycin C (MMC) 10 mg/m2 D2 and 5-fluorouracil (5-FU) 30 mg/kg/day as a continuous infusion D1-5 in 4-5 week cycles. It was designed as an alternative to treating patients with standard single agents in sequence, thereby preventing the testing of new drugs as part of primary therapy. Median survival was 12+ months for patients with measurable and 18+ months for patients with nonmeasurable colorectal cancer. It was 9+ months from the onset of secondary chemotherapy. Toxicity included severe thrombocytopenia (50%), severe leukopenia (25%), and moderate stomatitis (50%). Only one instance of leukopenia was life-threatening. The MMC and 5-FU infusion skeleton provides an attractive strategy for testing new drugs as primary therapy. HexMF itself has a potentially broad antitumor spectrum and excellent acceptance by patients. It is suitable for additional phase II trials.
Altretamine↗
Phase II trial of combination chemotherapy for pancreatic cancer with 5-fluorouracil, mitomycin C, and hexamethylmelamine.
A combination consisting of hexamethylmelamine 150 mg/m2 D2-15, mitomycin C 10 mg/m2 D2 and 5-fluorouracil 30 mg/kg/day as a continuous infusion for 5 days, in 4-5 week cycles, underwent phase II trial as primary therapy for 21 patients with regional and metastatic cancer of the pancreas. Median survival from the onset of therapy was 43 weeks. There were 2 complete responses, 4 minor responses and 6 stable diseases for more than 6 months. Nonambulatory patients were among the responders. There was only 1 life-threatening toxicity (thrombocytopenia) and only 33% of patients had clinically silent severe hematological toxicity. The regimen is well tolerated, active and associated with excellent survival. This regimen is suitable for further confirmatory trials.
Altretamine↗
Hexamethylmelamine, cyclophosphamide, adriamycin, cis-platinum chemotherapy as initial and second-line treatment of advanced ovarian carcinoma.
Thirty-six patients with advanced/recurrent epithelial ovarian carcinoma were treated with a combination of hexamethylmelamine, cyclophosphamide, adriamycin, and cis-platinum. In the group of 23 previously untreated patients, 10 of 12 (83%) with measurable disease had objective responses (7 complete, 3 partial). The median survival of the 23 patients exceeded 18 months. After approximately 1 year of chemotherapy, 9 patients with no clinical evidence of disease had a 'second look' laparotomy; 6 of these patients were disease-free. Two of the 6 patients with surgically documented complete responses had bulky (greater than 5 cm) disease prior to initiation of chemotherapy and remained disease-free at 22 and 50 months. One of the 6 patients relapsed 5 months after a negative second look. The other patients were alive and disease-free at 18, 46, and 51 months. Only 4 of 13 melphalan-resistant patients (31%) demonstrated an objective response to the 4-drug combination. The median survival was 13 months.
Adult↗
Primary treatment of regional and disseminated pancreatic cancer with hexamethylmelamine, mitomycin C and 5-fluorouracil infusion.
Hexamethylmelamine, mitomycin C and 5-fluorouracil infusion (HexMF) achieved a median survival of 9 months for the 45 patients with either metastatic stage III or unresectable stage II carcinoma of the pancreas. Fifteen percent survived 2 years. Of 32 patients with measurable tumors, 7 had partial and 3 had minor responses (31%); an additional 44% has stable disease for 3 months or more. Response was associated with a 17-month median survival. These findings are indications for further evaluation of both dosage-intensive 5-fluorouracil infusions alone and HexMF as an alternative to streptozotocin- or adriamycin-containing regimens. Patients with nonmeasurable disease are candidates for survival-oriented phase III studies.
Altretamine↗
Long-term follow-up of patients with advanced ovarian carcinoma treated with debulking surgery and chemotherapy consisting of cisplatin, doxorubicin, and cyclophosphamide. Gynecologic Oncology Group of the Comprehensive Cancer Center.
Between June 1980 and December 1984, 88 patients with stage III-IV ovarian carcinoma were entered in a study evaluating the role of debulking surgery and chemotherapy consisting of cyclophosphamide, doxorubicin, and cisplatin intravenously on day 1, every 4 weeks (CAP-1). The results after a median follow-up of 62 months (range 41-93 months) are presented. The median survival of all patients was 24 months (30 alive, 58 dead). The 5-year progression-free survival of all patients was 27% and the overall survival was 33%. Of patients with stage III disease debulked to lesions less than or equal to 1.5 cm before the initiation of chemotherapy (n = 34) the 5-year progression-free survival was 52%. Of 31 patients with a histologically documented complete response the median survival was 55+ months; 9 (29%) of them relapsed as opposed to 8 of 10 achieving microscopic residual disease at second look. Of 22 patients with stage IV disease, 20 died. This report confirms that patients who have undergone surgical removal of of bulk tumor and who achieve a complete remission have an improved survival outcome.
Altretamine↗