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At least 73 records · Page 4Linked to original sources
PubMed1983

A randomized comparison of melphalan versus melphalan plus hexamethylmelamine versus adriamycin plus cyclophosphamide in ovarian carcinoma.

A prospective randomized study was conducted in women with suboptimal (greater than or equal to 3 cm residual) Stage III, Stage IV, and recurrent ovarian adenocarcinoma to determine if combination chemotherapy is more effective than melphalan alone in achieving remission and improving survival. Of 233 evaluable patients with measurable disease, there were 64 treated with melphalan alone, of whom 20% achieved a clinical complete response and 17%, a partial response. Of the 97 patients receiving melphalan plus hexamethylmelamine, 28% achieved complete response compared with 32% of 72 patients given Adriamycin plus cyclophosphamide. The partial response rates for the combinations were 24% and 17%, respectively. The effect of these treatments was assessed in an additional 136 evaluable patients without measurable disease by progression-free interval and duration of survival. After statistically adjusting for distribution of cell type and grade, the clinical complete response rate for Adriamycin and cyclophosphamide (32%) in measurable cases was significantly higher (P = 0.04) than for melphalan alone. However, this combination did not improve median survival (12.3, 13.5, and 14.2 months, respectively, for M, M + H, and A + C). None of the other parameters showed a statistically significant advantage for combination chemotherapy, but the combinations caused more hematologic and gastrointestinal toxicity.

Adenocarcinoma↗
PubMed1983

Cis-platin based combination chemotherapy for advanced ovarian cancer. High overall response rate with curative potential only in women with small tumor burdens.

Thirty-eight women with advanced ovarian cancer were given monthly cycles of intravenous cyclophosphamide, Adriamycin (doxorubicin) and cis-platin, and oral hexamethylmelamine. Of 26 with tumor which would be evaluated for response, 42% had complete remission and 50% partial remission. Median time to disease progression from entry for all 38 patients was 13 months, and median survival 23.5 months. The bulk of tumor at the time chemotherapy was begun was the only significant prognostic factor for time to disease progression and survival. Of the seven women surviving free of disease a median of three years later, five had no mass greater than 2 centimeters in diameter at entry. Toxicity was predominantly myelosuppression and vomiting, with mild peripheral neuropathy in 27% and no significant renal or cardiac toxicity. The response rate of 92% is much higher than that previously reported with melphalan, and the survival considerably longer. The toxicity is acceptable, given the substantial improvement in results.

Adult↗
PubMed1984

Combination chemotherapy with or without hexamethylmelamine in alkylating-agent resistant ovarian carcinoma.

The study was designed to determine the efficacy of a two-drug and three-drug combination chemotherapy regimen for patients with advanced epithelial ovarian carcinoma resistant to alkylating monotherapy. Patients were randomized to receive either Adriamycin (doxorubicin) and cis-diamminedichloroplatinum(II) (AP) repeated every 3 weeks, or AP plus hexamethylmelamine (HAP) repeated every 5 weeks. Forty-five patients were evaluable for response and 49 for survival. No significant differences were found between the treatment groups as to response rate, progression-free survival, and survival. A remission was achieved in 20% of the patients and stable disease in another 20%. Median progression-free survival of all patients was only 4 months (median survival, 6 months). All patients showed progressive disease within 13 months after the onset of chemotherapy. Patients responding to treatment and those with an interval of more than 2 years between the initial diagnosis and cancer recurrence, experienced prolonged survival. Two conclusions can be drawn from the results of this study; neither of the regimens is superior to the other, and the effect of both in alkylator-resistant patients with ovarian cancer are meager. In studies on salvage chemotherapy, to the contrary, these combinations induced remissions in more than 40% of the patients. This difference in response rate might be due to differences between the prognostic factors of the patient populations. Better results are to be expected when these drugs are used in initial drug programs for previously untreated patients.

Altretamine↗
PubMed1984

"Second-effort" surgical resection for bulky ovarian cancer.

Eighteen women with bulky ovarian cancer at the start of chemotherapy were brought to second laparotomy after 6 months of combination chemotherapy in an effort to resect previously unresectable tumor masses. Only one of 18 had significant resection of bulk tumor such that no gross tumor was remaining, although 8 of 15 had the residual uterus removed and 6 of 10 had resection of residual ovary or ovaries. Failure to resect tumor was due to absence of any gross tumor (33%), presence of myriad small seedlings not amenable to resection (22%), or massive residual tumor (18%). Partial resection was accomplished in 22%, but all relapsed promptly in spite of continued aggressive therapy with drugs and whole abdominal irradiation. It is concluded that 6-month "second-effort" surgical resection is unlikely to benefit many women with bulky ovarian cancer, and that surgical resection must be attempted early in the course of the disease if it is to be effective.

Adult↗
PubMed1985

HAC-Cytoxan (cyclophosphamide) chemotherapy for ovarian carcinoma. Alternating chemotherapy with intensification.

Twenty-two previously untreated patients with adenocarcinoma of the ovary were treated with 28 day cycles of hexamethylmelamine, Adriamycin (doxorubicin), and cisplatin (HAC) for 9 months followed by three monthly cycles of intense intravenous cyclophosphamide. An overall response frequency of 82% (18/22) was achieved. Complete pathologic responses (CPR) documented by second look operations were found in 50% (11/22); however, patients considered to be free of disease (prolonged complete clinical response refusing "second look" and CPR) totaled 59%. Median survival has not been reached after a median follow-up of 34 months. No major or life threatening toxicity was encountered. HAC followed by cyclophosphamide is a highly effective regimen that may be easily administered on an outpatient basis with comparatively little toxicity.

Adenocarcinoma↗
PubMed1986

A 10-year experience with combined modality therapy for stage III small cell lung carcinoma.

During the past 10 years, 240 patients with Stage III small cell lung carcinoma (SCLC) were treated with one of five chemotherapy programs plus thoracic irradiation. In addition, prophylactic cranial irradiation was administered concurrently with thoracic irradiation to 194 patients receiving CAML-HC, VCAM, or MOCA. Seventy-two patients had disease confined to the chest (Stage IIIM0), 30 patients had disease in the chest plus ipsilateral supraclavicular nodal involvement (Stage IIIM0SCN+), and 138 patients had distant metastatic disease (Stage IIIM1); the median survivals were 15.2 months, 12.6 months, and 8.4 months, respectively. The overall complete response rate was 30% and the overall response rate (complete and partial) was 76%. The overall response rates by stage were 86% for Stage IIIM0, 90% for Stage IIIM0SCN+, and 67% for Stage IIIM1. Eight patients (3%) were alive and free of disease at 24 months. Due to continued disease relapse in this group (four of eight patients), long-term survivors should not be identified for a minimum of 3.5 years from the time of initial therapy. Prophylactic cranial irradiation (PCI) effectively reduced the incidence of central nervous system (CNS) relapse in patients with a complete response to therapy (44% relapse without PCI versus 13% relapse with PCI, P less than 0.01). More effective chemotherapy is required for the successful treatment and improved long-term survival of patients with SCLC.

Altretamine↗
PubMed1987

Treatment of advanced ovarian cancer with sequential combination chemotherapy.

Fifty previously untreated patients with advanced or recurrent ovarian cancer (FIGO Stages III and IV) were treated with alternating combination chemotherapy. This consisted of high-dose doxorubicin (70 mg/m2) and cisplatin (100 mg/m2) alternated with CHF (cyclophosphamide, hexamethylmelamine, and 5-fluorouracil). Toxicity (myelosuppression, nephropathy, and neuropathy) was infrequent and mild. Clinical response rates were high (94% response, 62% complete clinical response), but the majority of patients had residual intraabdominal disease at second-look surgery (75%). Thirteen patients (26%) are alive after 4 years of observation (minimum follow-up). Survival was adversely influenced in patients who were older than 70, had Stage IV disease, residual tumor bulk greater than 2 cm, and who failed to achieve complete clinical remission. The median duration of survival (28 months) and percentage of long-term survivors appear similar to that in other platinum-based chemotherapy studies. Although the role of alternating combination chemotherapy in epithelial ovarian cancer remains undefined, it is likely that an alternate approach will be necessary to markedly improve survival rates for patients with this disease.

Adult↗
PubMed1988

Treatment of advanced ovarian cancer with surgery, chemotherapy, and consolidation of response by whole-abdominal radiotherapy.

Between April 1981 and June 1985, 195 patients with ovarian cancer, International Federation of Gynecology and Obstetrics (FIGO) Stages IIB, IIC, III, and IV, entered a trial that consisted of surgery and chemotherapy with cisplatin (P) and melphalan (PAM) with or without hexamethylmelamine (HexaPAMP or PAMP regimens) every 4 weeks for 6 cycles. Because the intent was to study the outcome by treatment after evaluation of first-line chemotherapy, patients were evaluable only if the response was assessed by a second-look operation or if measurable disease progression was documented. One hundred fifty-eight patients (81%) were evaluable for response. Forty-five (28%) achieved pathologically confirmed complete remissions (pCR), and 24 of these patients received whole-abdominal radiation (WAR) for consolidation of response. Five patients with complete remission after WAR relapsed, as did nine of the 21 with complete remission who had not undergone WAR. The 3-year time to progression percentage (TTP +/- SE) from second-look operation was 70% +/- 7% for all patients who achieved pCR, 83% +/- 8% for those who received WAR, and 49% +/- 15% for those who did not receive WAR (this was not a randomized comparison). The 3-year TTP percentage for the 49 partial responders was 21% +/- 6%, identical for the 19 who had WAR and the 30 who had no radiation therapy. Additional or alternative methods for consolidation of pCR are needed since patients continue to relapse despite optimal initial response to therapy.

Abdomen↗
PubMed1990

Incidence of neuropathy in 395 patients with ovarian cancer treated with or without cisplatin.

In two consecutive trials, a total of 395 patients with ovarian cancer were treated with a combination of hexamethylmelamine, cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapeutic regimens including cisplatin or without this drug. With respect to neurotoxicity, 387 patients were fully eligible. The median follow-up for survival was 45 months. Neurotoxicity in any grade of severity developed in 47% of the patients treated with a cisplatin-containing regimen and in 25% of those treated with the non-cisplatin-containing regimen. The severity of neurotoxicity was much higher, however, in the cisplatin-treated patients. Neurotoxicity-free survival decreased below 50% at cumulative doses of cisplatin between 500 and 600 mg/m2. No additional effect of hexamethylmelamine on the incidence or severity of neurotoxicity could be demonstrated. In patients who survived for more than 5 years, the incidence of cisplatin neuropathy was 61%. Prognostic variables (age, International Federation of Gynecology and Obstetrics [FIGO] stage, performance status, and others) possibly associated with high-risk subgroups could not be identified. The only consistent factor correlated with neurotoxicity was the total dose of cisplatin received.

Altretamine↗
PubMed1984

The effect of lithium carbonate on chemotherapy-induced neutropenia and thrombocytopenia.

Lithium carbonate ameliorates neutropenia associated with cancer chemotherapy. The effect of lithium on platelet suppression has not, however, been well established. In the present study, five patients with ovarian carcinoma received daily lithium during alternate cycles of treatment with hexamethylmelamine, cyclophosphamide, adriamycin, and cis-platinum. Analysis of myelosuppression was performed on 24 paired consecutive cycles given at identical doses, one with and one without lithium. During lithium cycles, nadir leukocyte, neutrophil, and platelet counts were significantly higher (P less than 0.01, less than 0.01, less than 0.05 respectively) and the interval between treatments was shorter (P less than 0.01). One patient who has received 11 cycles of chemotherapy continues to receive 100% doses owing to the beneficial effect of lithium on chemotherapy-induced thrombocytopenia. Lithium was poorly tolerated by some patients because of either tremor or nausea and vomiting, in spite of nontoxic serum lithium levels. The amelioration of drug-induced platelet suppression as well as neutrophil suppression noted in this study suggests that lithium's effect on hematopoiesis is not limited to stimulation of neutrophil production. The ability of lithium to decrease chemotherapy-induced myelosuppression suggests that lithium administration may facilitate escalation of chemotherapy doses in selected patients.

Agranulocytosis↗
PubMed1993

Second-line chemotherapy for recurrent carcinoma of the ovary.

Despite relatively high response rates to chemotherapy for ovarian carcinoma, most patients eventually will have progressive disease that will require additional therapy. Most efforts to study such second-line or "salvage" chemotherapy have been single-arm trials of small numbers of patients, which report widely variable response rates, relatively short response durations, and short survival times. Only recently have certain critical patient characteristics been recognized as important in determining appropriate therapy as follows: (1) the extent and volume of disease at recurrence and (2) the type and duration of response to prior chemotherapy. Patients with small-volume disease confined to the peritoneal cavity have a far better chance of achieving a response to second-line chemotherapy with subsequent prolonged survival than do those with bulky disease or disease outside the abdomen. Perhaps even more critical is the distinction between those patients whose neoplasm is still "clinically sensitive" to the platinum-containing compounds (initial response to platinum-based therapy and relapse more than 6 months after cessation of treatment) and those with "clinically resistant" disease (progression during or within 6 months of front-line platinum-based therapy). Those considered clinically sensitive to platinum-based therapy should be retreated with a platinum-containing regimen at the time of recurrence. Those with evidence for resistance should receive alternative treatment with one or more drugs capable of inducing responses in such patients. These drugs currently include: taxol, ifosfamide, and hexamethylmelamine.

Altretamine↗
PubMed1989

Isoelectric focusing of membrane proteins: high resolution separation of myelin proteins.

A mixture of the nonionic detergent Triton X-100, the zwitterionic detergent 3-[(cholamidopropyl)dimethylammonio]-1-propanesulphonate (CHAPS), 9M urea and carrier ampholytes was found comparable to media containing sodium dodecyl sulfate in the capacity for solubilization of myelin proteins, including the highly hydrophobic proteolipid protein. The solubilized sample was incorporated into the polymerization mixture before moulding an ultrathin gel, with heat convection characteristics allowing a high wattage to be applied, thus allowing fast separation with high resolving power. Since the most basic protein in myelin focuses at a pH greater than 10, fast separation is essential in order to minimize decay of the cathodic end of the pH gradient.

Altretamine↗
PubMedDate not supplied

Advances in the chemotherapy of gynecologic malignancies.

Chemotherapy is playing an ever increasing role in the treatment of patients with the common gynecologic malignancies, including ovarian, cervical cancer, and endometrial cancer. Chemotherapy has its most defined role in the treatment of patients with ovarian cancer where virtually all patients will receive cytotoxic chemotherapy. There are four major areas of research in chemotherapy in gynecologic malignancies. In retrospective studies it has been demonstrated that dose intensity is an important factor in maximizing response rates. Clinical studies are now prospectively evaluating the importance of dose intensity, particularly with the new platinum analogue carboplatin. In addition, it has been demonstrated in endometrial cancer and cervical cancer that patients with poor prognostic features such as high grade tumours and large volume disease have a low probability of cure by standard modalities such as surgery and radiation. In this group of patients combined modality approaches are being evaluated. In addition, regional therapy, either in the form of intra-arterial therapy for patients with cervical cancer or intraperitoneal therapy for patients with ovarian cancer, is being investigated. The primary factor limiting the effectiveness of chemotherapy in gynecologic malignancies is the development of drug resistance. It has recently been demonstrated that several drugs such as taxol, ifosfamide, and hexamethylmelamine have activity in patients who have had previous treatment with platinum-based compounds. In addition, the mechanism associated with the development of drug resistance in ovarian cancer have recently been identified. Clinical trials have been initiated with compounds such as buthionine sulfoximine in an attempt to specifically reverse resistance associated with alkylating agents and platinum compounds.

Alkaloids↗
PubMed1975

Complexation in formulation of parenteral solutions: solubilization of the cytotoxic agent hexamethylmelamine by complexation with gentisic acid species.

The apparent solubility of hexamethylmelamine in aqueous solutions suitable for intravenous use was increased by complexation with gentisic acid. Studies were carried out in the pH 0-8 range. Unprotonated hexamethylmelamine did not form complexes with the gentisate ion, while the hexamethylmelammonium ion appeared to form several different complexes with both the gentidate ion and gentisic acid. Two different solid complexes were isolated and characterized. The solubility increases observed at pH 3.5-5.0 are described by mathematical relationships involving the stability constants of some postulated complex species. From these results, sultable formulations for use as parenteral solutions are proposed. The increase in the apparent aqueous solubility of hexamethylmelamine in such formulations may range from five- to 90-fold, depending upon the pH and total gentisateion concentrations.

Altretamine↗
PubMed1976

Studies and characterization of a murine neuroblastoma model.

Clinical chemotherapy in the treatment of neuroblastoma is undergoing further evaluation. Chemotherapeutic agents, cyclophosphamide, vincristine, and hexamethylmelamine, were investigated in a murine neuroblastoma model that, in part, histologically and morphologically resembles the human tumor. The tumor was inoculated subcutaneously (SC), intramuscularly (IM), intraperitoneally (IP), intrarenally (IR). Growth of tumor was observed at all sites, as well as the appearance of metastases. Maximal survival of 32 +/- 1 days was seen (SC) and the minimum was 15 +/- 1 days (IR) (p less than 0.05). Corresponding survival rate for IM was 26 +/- 1 days and IP 21 +/- 1 days. For this reason SC was selected for drug testing. Cyclophosphamide 100 mg/kg/week showed the most favorable results, as determined by autopsy status with fewer tumors and a greater tumor weight decrease over time. This agent also showed a significantly longer survival in comparison to all other drugs (p less than 0.0001). The results with vincristine and hexamethylmelamine in the dose ranges employed differed little from the placebo, except for the finding of a slight decrease in body weight at autopsy.

Altretamine↗
PubMed1982

Hexamethylmelamine and melphalan as salvage therapy in advanced ovarian carcinoma.

Ten patients with advanced ovarian carcinoma were treated with hexamethylmelamine and melphalan after failing first-line combination chemotherapy. In eight patients residual disease was evident only at second-look laparotomy. Surgical debulking was accomplished in four patients but only two patients had residual disease of less than 2 cm. Two of these four patients are alive without evidence of disease to 20 and 24 months. The remaining patients have expired (median survival 6 months). The combination of hexamethylmelamine and melphalan after surgical debulking at second-look operation may improve the salvage of patients with advanced ovarian carcinoma.

Adenocarcinoma, Papillary↗
PubMed1983

Alternating multiagent chemotherapy for advanced ovarian cancer.

A chemotherapy regimen consisting of hexamethylmelamine (H) 150 mg/m2 orally days 1-14, cyclophosphamide (C) 500 mg/m2 IV day 1 of a 28-day cycle with Adriamycin (A) 40 mg/m2 IV day 1 alternating with cis-diamminechloroplatinum (C-P) 50 mg/m2 IV day 1 every other cycle was administered to 29 patients with advanced epithelial ovarian cancer. Toxicity to this regimen included alopecia, nausea, and vomiting in all patients. Mild paresthesias occurred in four patients. Hematologic toxicity required only minimal dose modification. There was no cardiac, renal, or auditory toxicity. The clinical response rate of 55% and median survival of 14 months compare favorably with that of other reported series. This chemotherapy regimen seems to be well tolerated without jeopardizing the patients' response.

Adenocarcinoma↗