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PubMed1991

Antitumor effect of combination of cyclophosphamide, adriamycin and platinum (CAP) versus cyclophosphamide, adriamycin and 5-fluorouracil (CAF) in metastatic breast cancer.

The aim of the present study was to evaluate the antitumor effect of two drug combinations in disseminated breast cancer. Eighty-one patients divided into two groups entered this nonrandomized study. Group 1 included 32 patients treated with CAP combination: Cyclophosphamide--200 mg/m2 on days 1, 3 and 5 + adriamycin--40 mg/m2 on day 1 + cisplatin--30 mg/m2 on days 1, 3 and 5. Group 2 included 49 patients treated with CAF combination: Cyclophosphamide--100 mg/m2 on days 1 to 14 + adriamycin--30 mg/m2 on days 1 and 8 + 5-fluorouracil--500 mg/m2 on days 1 and 8. All patients had at least 2 courses of chemotherapy. In Group 1 the remission rate was 50% (16 patients) including 3 complete (9%) and 13 partial remissions (41%). In Group 2 the remission rate was 39% (18 patients) with 8 complete (16%) and 10 partial remissions (23%). The analysis of duration of the remissions showed a tendency towards longer duration after treatment with CAP combination (25 versus 15 months for the complete remissions, and 14 versus 11 months for the partial remissions).

Adult↗

PubMed1986

Effects of Mega-COMLA (cyclophosphamide, cytarabine, vincristine, and methotrexate followed by leucovorin and prednisone) plus CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) in the treatment of lymphoid neoplasms with very poor prognosis.

Treatment results remain very poor for some clinical and histopathologic subsets of patients with aggressive non-Hodgkin's lymphoma. We treated 21 such patients with a high-dose combination chemotherapy regimen [Mega-COMLA (cyclophosphamide, cytarabine, vincristine, and methotrexate followed by leucovorin and prednisone) + CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)] in an attempt to improve disease-free survival. Neoplasms were classified using the Lukes-Collins system. Eight patients had T-cell lymphomas (convoluted lymphocytic lymphoma, four patients; T-cell lymphoma/leukemia, one; and peripheral T-cell lymphoma, three), eight had B-cell lymphomas (immunoblastic sarcoma, five patients; small noncleaved follicular center cell, one; and large noncleaved follicular center cell, two), and five had nontypable large noncleaved cell lymphomas. All patients were previously untreated; 18 of 21 patients had clinical stage III or IV disease. Following induction therapy (4-8 weeks' duration), 16 patients (76%) achieved complete remission, while three had partial remission. Two patients died of sepsis during induction therapy. Eleven of 16 complete responders (69%) remain in complete remission after a median follow-up of 35 months. The actuarial 3-year survival rate is 51% for the entire group. Myelosuppression with this regimen was severe and prolonged, with a median duration of neutropenia (less than 500 cells/microliter) of 14 days. Seven patients (33%) developed severe neuropathy following induction treatment. High-dose induction therapy with this regimen resulted in a high complete remission rate with manageable toxicity. Survival results are encouraging when compared retrospectively to our patients with similar poor-prognosis histologies treated with standard combination chemotherapy. However, the value of this intensive therapy, relative to newer ("third-generation") regimens, can only be established by prospective randomized studies.

Actuarial Analysis↗

PubMed1988

Cytostatic treatment of glomerular diseases. V. Treatment of glomerulonephritis with cyclophosphamide plus prednisone, azathioprine plus prednisone and cyclophosphamide as monotherapy. A comparative study. A report from a Copenhagen Study Group of Renal Diseases.

Thirty-two patients suffering from biopsy-proven glomerulonephritis with proteinuria greater than or equal to 1.2 g/24 hours and/or creatinine clearance less than 50% of normal value were treated for 6 weeks with prednisone plus cyclophosphamide (C+P), azathioprine (A+P) or cyclophosphamide as a monotherapy (C). The effect of the treatment was evaluated after 6 and 16 weeks. The results were entered consecutively in a sequential analysis. The three treatment regimes were compared mutually as well as with the results of 16 weeks' treatment with C and placebo, published previously. Six weeks' treatment with C+P or A+P was superior to C and at least as efficient as 16 weeks' C treatment. C treatment for 6 weeks was less efficient than 16 weeks' C treatment. The side-effects of the 6 weeks' A+P or C+P treatment were fewer and less serious than those reported from the long-term C treatment.

Adult↗

PubMed1988

Administration of radiation or cyclophosphamide versus alternated radiation and cyclophosphamide treatment of primary tumor and pulmonary metastases.

The experimental tumor 3924A in ACI rats metastasizes to the lungs, but this is rarely apparent unless the life span of the animal is increased by treatment of the tumor. Pulmonary metastases were prevalent among animals given radiation daily or in multiple fractions per day over periods of 3-4 weeks at total doses ranging from 3,000 to 11,250 rad. Multiple doses of cyclophosphamide, each at the level that was lethal to 10% of the animals, did not cure the primary tumor but appeared to delay the appearance of metastases. Treatment schedules that alternated the delivery of multiple 250-rad fractions of radiation during 2-day periods with cyclophosphamide at a dose of 150 mg/kg for a total of three courses were effective in curing the primary tumor and eliminating pulmonary metastases.

Animals↗

PubMed1986

[Results of clinical trials with a CMitF (cyclophosphamide, mitoxantrone, and 5-fluorouracil) regimen versus a CAF (cyclophosphamide, adriamycin, and 5-fluorouracil) regimen in advanced/relapsed breast cancer].

Randomized clinical trials were conducted in patients with advanced/relapsed breast cancer, using CMitF (mitoxantrone, cyclophosphamide, and 5-fluorouracil) regimen in comparison with CAF (cyclophosphamide, adriamycin, and 5-fluorouracil) regimen. The response rate was 50% (13/26) for the CMitF group and 50% (10/20) for the CAF group. Classified by disease site, CAF group showed a tendency for a higher response rate in soft tissue, but in bone and viscera the rates were similar for both regimen groups. The median weeks to response (range) was 5 (3-21) weeks for the CMitF group, and 8 (3-22) weeks for CAF group, a tendency for slightly earlier response thus being shown in the CMitF group. The median duration of response (range) was 10 (4-47) weeks for the CMitF group, and 9 (4-50) weeks for CAF group, whereas by the method of Kaplan-Meier, at 40 weeks after the start of therapy, the proportion showing response still continued to be 60% for the CMitF group, which was a higher rate than the 27% for CAF group. The survival rate at 48 weeks was for both groups with no difference shown. Leukopenia, gastrointestinal symptoms and alopecia were major side effects in both groups, but the incidence and severity grade of gastrointestinal symptoms (nausea and vomiting) and alopecia were significantly less in the CMitF group than in CAF group. In both groups, the WBC nadir was 2,100/microliter and the time to nadir was 14 days, with no difference shown in hematological toxicity between the two groups. No severe cardiac, hepatic, or renal toxicity was noted.

Adult↗

PubMed1987

The effect of the rat-cyclophosphamide serum on the rat hematopoietic tissue recovery, previously damaged by cyclophosphamide or by gamma-irradiation.

The effect of post-cyclophosphamide serum (post-CY serum) humoral activity in vivo, on the rat hematopoietic regeneration after damage either by cyclophosphamide (CY) or by gamma-irradiation was investigated. Three experimental groups of rats were studied. The first group was treated by a single high dose of CY (200 mg/kg), the second group was whole body irradiated by 6.5 Gy, and the third group was whole body irradiated by 3.5 Gy. Each group was subdivided into three subgroups. The first among subgroups received immediately after damage 0.5 cc post-CY serum, the second received 0.5 normal rat sera per animal. The third subgroup of rats was used as control. Post-CY sera were collected from the Wistar rats, 2.5 months old 48 hours after the treatment by high single dose by CY (300 mg/kg). Post-CY serum activity in comparison to normal serum activity was evaluated in vivo conditions. In order to take samples of peripheral blood, spleen and bone marrow, the animals were sacrificed 24 hours, 48 hours, 72 hours and seven days after treatment. The assessment of post-CY sera effect is accomplished by measuring of the proliferative capacity of splenic, as well as bone marrow cells, and by means of the RBC and WBC counts. The results obtained indicate substantial stimulative and proliferative activity of the post-CY sera, when compared to normal sera, particularly in the animals previously damaged with CY.

Animals↗

PubMed1985

Comparison of cyclophosphamide plus cisplatin versus hexamethylmelamine, cyclophosphamide, doxorubicin, and cisplatin in combination as initial chemotherapy for stage III and IV ovarian carcinomas.

Among 187 women with stage III and IV ovarian carcinoma who participated in this comparative clinical trial, 181 were eligible for analysis. Of these patients, 89 received monthly treatment with CP [cyclophosphamide (1 g/m2) plus cisplatin (60 mg/m2)] and 92 received monthly treatment with HCAP [hexamethylmelamine (150 mg/m2/day X 7), cyclophosphamide (400 mg/m2), doxorubicin (30 mg/m2), and cisplatin (60 mg/m2)]. All treatments were administered iv on Day 1 of each monthly treatment cycle, except for hexamethylmelamine, which was administered orally on Days 2-8. With a median follow-up time of 30 months, survival curves for the two treatment groups were almost identical, as were their times to progression [estimated median survival, 24.6 months (Kaplan-Meier)]. Patient characteristics which significantly influenced survival were age, degree of histologic differentiation, extent of residual disease, stage of disease, and histologic type. Results of posttreatment laparotomies have been equal for the two treatment groups. Toxic effects of the two regimens have been similar, except for more frequent, more severe, and earlier neurotoxicity among patients treated with HCAP. Of the two regimens, CP has the better therapeutic index.

Adult↗

PubMed1982

Randomized study comparing doxorubicin, cyclophosphamide, vincristine, methotrexate with leucovorin rescue, and cytarabine (ACOMLA) with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-B) in the treatment of diffuse histiocytic lymphoma.

Two combination chemotherapy programs, ACOMLA (doxorubicin, cyclophosphamide, vincristine, methotrexate and leucovorin rescue, and cytarabine) and CHOP-B (cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin), were evaluated in 29 prospective randomized patients with advanced diffuse histiocytic lymphoma. A complete response was achieved in 13 of the 15 patients (87%) treated with CHOP-B and in nine of the 14 patients (64%) treated with ACOMLA. The overall complete response rate was 75%. Two patients treated with ACOMLA and none of the CHOP-B-treated patients have relapsed. Median followup is 32 months for ACOMLA patients and 26 months for CHOP-B patients. Actuarial freedom from relapse at 2 years is 49.9% for ACOMLA and 93.3% for CHOP-B (P = 0.04). Toxicity was substantial, with eight nonfatal episodes of sepsis and three drug-related deaths. There have been no central nervous system relapses. Although patients treated with CHOP-B have a better response rate, the small numbers of patients treated to date preclude definitive conclusions.

Antineoplastic Agents↗

PubMed1984

A randomized comparison of cyclophosphamide-mitoxantrone-5-fluorouracil v cyclophosphamide-doxorubicin-5-fluorouracil in advanced breast cancer: preliminary observations.

Forty-four patients with measurable metastatic breast cancer have been entered in a randomized study comparing mitoxantrone to doxorubicin as a component of front-line combination chemotherapy. Patients were stratified according to whether or not they had previously received adjuvant chemotherapy. Initial doses of cyclophosphamide and 5-fluorouracil were 500 mg/m2 for both regimens, with either mitoxantrone, 10 mg/m2, or doxorubicin, 50 mg/m2. All drugs were given on day 1 only, with treatments repeated every 3 weeks. Doses were adjusted according to blood count nadirs. Responses have been observed in both of the treatment groups, though it is too early to determine the relative efficacy of the two regimens. Toxicity was comparable on the two treatment regimens except that far less alopecia and stomatitis were associated with the mitoxantrone therapy. No congestive heart failure has been seen. The combination of cyclophosphamide-mitoxantrone-5-fluorouracil is reasonably well tolerated, with myelosuppression being dose limiting. In both treatment groups of this study, reliance on the leucocyte count, rather than the granulocyte count, as a basis for dose alteration or treatment delay would lead to excessive dose reductions, many fewer dose escalations, and much more treatment delay.

Anthraquinones↗

PubMed1984

Cisplatin-MECY (methotrexate-leucovorin rescue plus cyclophosphamide) versus cisplatin-CHAD (cyclophosphamide, hexamethylmelamine, doxorubicin, and cisplatin) as initial chemotherapy in stage III-IV ovarian adenocarcinoma.

Thirty-three patients with advanced-stage ovarian adenocarcinomas, with no prior chemotherapy, were treated with weekly cisplatin (DDP) for four courses followed by five monthly courses of one of two randomly assigned multidrug combinations. These combinations were high-dose methotrexate-leucovorin plus cyclophosphamide (MECY) or cyclophosphamide, hexamethylmelamine, doxorubicin, and DDP (CHAD). Patients with no clinically measurable disease after 6 months of therapy were evaluated by laparoscopy. In the absence of disease progression at the time of the laparoscopy the study design called for a repeat cycle of four weekly DDP courses and another five monthly courses of the assigned multidrug combination. All patients with no evidence of disease after 1 year of treatment had a second-look laparoscopy which, if negative, was followed by a second-look laparotomy. This report includes all of the consecutively entered patients observed for a minimum of 1 year or to death. DDP-MECY and DDP-CHAD were similarly active for overall response rates and complete response rates according to laparoscopic criteria. However, DDP-MECY had a statistically significantly lower relapse rate (P less than 0.02) and a statistically significantly higher negative second-look laparotomy rate than did DDP-CHAD. Using all entered patients, with no exclusions from analysis, eight of 17 patients (47%) treated with DDP-MECY had negative second-looks after 1 year of treatment. This compares with one of 16 (6%) negative second-looks in patients treated with DDP-CHAD (P less than 0.02). The high negative second-look rate with DDP-MECY is exciting. Positive cytologic washings at the 6-month laparoscopic evaluation were highly predictive that residual disease would be found at the 1-year second-look surgery. Only one patient with positive peritoneal cytology after 6 months of treatment was found to have a negative second-look after 1 year of therapy.

Adenocarcinoma↗

PubMed1984

Polychemotherapy in ovarian cancer: treatment with Adriamycin, BCNU and cyclophosphamide vs. Adriamycin and cyclophosphamide.

The authors compared both therapeutic efficacy and toxicity of two different treatment regimens: ABC = adriamycin, nitrogen mustard (BCNU) and cyclophosphamide (CTX) vs. AC = adriamycin and cyclophosphamide in ovarian cancer. Thirty-one patients were entered under treatment plan ABC and 26 under treatment plan AC simultaneously. Therapeutic evaluation was subdivided into different risk groups (adjuvant therapy, residual disease less than or greater than 2 cm). A similar result could be noted in the two different treatment regimens. Toxicity was more severe and frequent in the group treated with BCNU. The AC regimen was preferred because of its lower incidence of side-effects and for its easier mode of administration.

Adenocarcinoma↗

PubMedDate not supplied

[Factors responsible for increasing the cytogenetic effectiveness of cyclophosphamide administered to irradiated animals. Mutagenic effect of cyclophosphamide on irradiated and intact cells in culture].

The frequency of cyclophosphamide-induced chromosome aberrations in preirradiated cultures of L-cells and embryonal rat fibroblasts has been estimated. The mutagen was subjected to nonenzymatic activation in solution at 37 degrees C. In contrast to the results previously obtained on animals we failed to observe any influence of preirradiation on the cytogenetic effect of cyclophosphamide.

Animals↗

PubMed1995

Randomized, comparative study of high-dose (with autologous bone marrow support) versus low-dose cyclophosphamide, cisplatin, and carmustine as consolidation to adjuvant cyclophosphamide, doxorubicin, and fluorouracil for patients with operable stage II or III breast cancer involving 10 or more axillary lymph nodes (CALGB Protocol 9082). Cancer and Leukemia Group B.

The prognosis for patients with primary breast cancer involving multiple axillary lymph nodes is poor. Only about 30% of patients remain disease-free at 5 years from diagnosis despite surgery, conventional-dose chemotherapy, and radiation therapy. In nonrandomized studies, the use of high-dose chemotherapy as consolidation therapy after standard-dose induction chemotherapy has resulted in an apparent improvement in disease-free survival rates to over 70%. These results have prompted the National Cancer Institute to sponsor large-scale, multicenter, randomized comparative trials of this strategy. This Intergroup Study (Cancer and Leukemia Group B 9082, Southwest Oncology Group 9114, and National Cancer Institute of Canada MA13) compares two treatment strategies in women with primary breast cancer involving 10 or more axillary lymph nodes. Arms A and B are identical in the use of four cycles of conventional therapy with cyclophosphamide and doxorubicin and fluorouracil, radiation therapy, and tamoxifen. The only difference between the two arms is the dose intensity of the cyclophosphamide, cisplatin, and carmustine given following conventional adjuvant treatment. Arm A dictates bone marrow, peripheral blood stem cell, and hematopoietic growth factor support and frequently requires a prolonged hospital stay with high resource utilization. Arm B, with its less dose-intensive therapy, requires considerably less support to apply the treatment. Because of the high cost of this therapy and the requirement for technology-intensive support, there has been considerable interest in economic outcome assessments.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1999

Prospective Randomized Study of Cyclophosphamide, Epirubicin, and 5-Fluorouracil versus Cyclophosphamide, Adriamycin, and 5-Fluorouracil in Advanced or Recurrent Breast Cancer.

BACKGROUND: Treatment with cyclophosphamide, adriamycin, and 5-fluorouracil (CAF), a widely used, potent regimen is sometimes restricted by the myelotoxicityand myocardiotoxicity of adriamycin (ADR). In a prospective randomized controlled study of patients with advanced or recurrent breast cancer, the efficacy and toxicity of a CEF regimen, in which epirubicin (EPI) was substituted for ADR, was compared with CAF. METHODS: 138 female patients under 75 years of age who had unresectable or recurrent breast cancer during the period from October, 1989 to September, 1991, were randomized to one of two treatment regimens. The first regimen consisted of cyclophosphamide 100 mg p.o. d1-14, adriamycin 30 mg/m(2) i.v. d1, 8 and 5-fluorouracil 500 mg/m(2) i.v. d1, 8 (CAF). In the second regimen, EPI 30 mg/m(2) i.v. d1, 8was substituted for ADR (CEF). Both regimens were delivered q4 weeks. RESULTS: Of 138 patients, 105 (CEF 56, CAF 49) were evaluable for response and survival, and all were evaluable for toxicity (CEF 68, CAF 70). The median course of lots CEF and CAF was 3 cycles. Response rates (complete response plus partial response) with CEF and CAF were 35.7% (20/56) and 36.7% (18/49), respectively. Adverse effects were similar in the two groups, but severe leukopenia (CEF 36.8%, CAF 64.3%) and hepatic toxicity (CEF 1.5%, CAF 12.9%) were encountered more frequently with CAF than with CEF. The duration of 50% survival was 135.9 weeks for CEF and 172.1 weeks for CAF (not significant). CONCLUSION: At an equal dose of EPI and ADR response rates and survival of the CEF group were similar to those of the CAF group, but adverse effects were fewer in the CEF group.

Journal Article↗

PubMed1979

Low dose chemotherapy of metastatic breast cancer with cyclophosphamide, adriamycin, methotrexate, 5-fluorouracil (CAMF) versus sequential cyclophosphamide, methotrexate, 5-fluorouracil (CMF) and adriamycin.

Seventy-eight advanced breast cancer patients with hormone-resistant disease or visceral metastases were randomized to receive either of two low dose regimens consisting of cyclophosphamide (C), methotrexate (M), 5-fluorouracil (F), and Adriamycin (A) as their initial chemotherapy. One group was treated with CAMF, and the other with CMF until progression, followed by A (CMF leads to A). C was given at 50 mg/m2, po, days 1-14; M at 20 mg/m2, F at 300 mg/m2, and A at 20 mg/m2, iv, days 1 and 8 of each 28-day cycle. The response rates for CAMF vs. CMF did not differ significantly (complete and partial responses-62% vs. 49%; stabilizations-23% vs. 31%). Responses by site of metasis, median times to progression and median survivals were similar for both groups. Poor and good risk partial responders had similar survivals. Twelve percent of CMF patients treated with Adriamycin at the time of progression had partial responses with an associated improved survival. Since CMF is as effective as CAMF, but has less toxicity, low dose therapy with CMF is more acceptable than CAMF as an initial chemotherapy regimen for metastatic breast cancer. Adriamycin may be reserved for subsequent regression induction.

Antineoplastic Agents↗

PubMed1997

A prospective, multicenter, randomized trial comparing steroids and pulse cyclophosphamide versus steroids and oral cyclophosphamide in the treatment of generalized Wegener's granulomatosis.

OBJECTIVE: To investigate the effectiveness and side effects of oral versus pulse cyclophosphamide (CYC) in combination with corticosteroids (CS) in the treatment of systemic Wegener's granulomatosis (WG). METHODS: Patients with newly diagnosed systemic WG were enrolled in a prospective, randomized trial. At the time of diagnosis, prior to randomization, every patient received a daily injection of methylprednisolone for 3 days, followed by daily oral prednisone (1 mg/kg/day) and a 0.7-gm/m2 pulse of CYC. Patients were then randomly assigned to receive either prednisone plus intravenous pulse CYC (group A) or prednisone plus oral CYC (group B) as first-line treatment. CYC was given for at least 1 year and was then progressively tapered and discontinued. RESULTS: Fifty patients were included in the study: 27 in group A and 23 in group B. At 6 months, 24 group A patients (88.9%) were in remission, versus 18 group B patients (78.3%). At the end of the trial, 18 group A patients (66.7%) and 13 group B patients (56.5%) were in remission. In group A, 66.7% of the patients experienced side effects, versus 69.6% in group B. Infectious side effects were significantly more frequent in group B (69.6%) than in group A (40.7%) (P < 0.05). The incidence of Pneumocystis carinii pneumonia was higher in oral CYC-treated patients (30.4%) than in pulse CYC-treated patients (11.1%). Nine group A patients (33.3%) and 10 group B patients (43.5%) died. Actuarial curves showed that relapses were significantly more frequent in group A (59.2%) than in group B (13%) (P = 0.02). CONCLUSION: Our results indicate that pulse CYC is as effective as oral CYC in achieving initial remission of WG and is associated with fewer side effects and lower mortality. However, in the long term, treatment with pulse CYC does not maintain remission or prevent relapses as well as oral CYC.

Administration, Oral↗

PubMed1981

Investigations on cyclophosphamide treatment during the preimplantation period. I. Differential sensitivity to maternal cyclophosphamide treatment.

To study the effect of cyclophosphamide (CPA) treatment of pregnant mice during the preimplantation period on different embryonic cells even before implantation, the cell numbers of the immunosurgically isolated inner cell mass (ICM) and the blastocyst total cell number (BTCN) were determined in late blastocysts. In animals treated at 2 P.M. on day 2 of pregnancy a dose-related reduction of the cell numbers was found for both ICM and BTCN in morphologically normal late blastocysts (day 4, 8 A.M.) at CAP doses of 20-60 mg/kg which did not induce embryonic death before implantation but did later during organogenesis. At identical CPA doses the reduction of the cell numbers of the ICM was significantly greater than that of the BTCN. These data provide evidence for a differential sensitivity of the two groups of cells in preimplantation mouse embryos (trophectoderm and ICM) to maternal CPA treatment even before implantation.

Animals↗

PubMed1984

Chemical characterization of ASTA Z 7557 (INN mafosfamide, CIS-4-sulfoethylthio-cyclophosphamide), a stable derivative of 4-hydroxy-cyclophosphamide.

The primary metabolite of cyclophosphamide (CP, 1), i.e. 4-hydroxy-CP 2, has high pharmacological activity, but it is a very unstable compound. Chemical approaches to the stabilization involved in the substitution of the hydroxy group at the C 4-position, especially by a sulfoalkylthio-moiety. Within this new class of compounds ASTA Z 7557 (2-(bis-(2-chloroethyl]-amino-cis-4-[2-sulfoethyl)-thio)-tetrah ydr o-2H-1,3, 2-oxaza-phosphorine-r-2-oxide cyclohexylamine salt, i.e. cis-4-sulfoethylthio-CP, cis-13) was chosen for further evaluation. Cis-13 was synthesized by condensation of compound 2 and 2-mercapto-ethanesulfonic acid cyclohexylamine salt 14 in aqueous acetone yielding the cis-isomer with high stereoselectivity. It is a white crystalline powder, m.p. 126-134 degrees C, stable at room temperature, with a solubility of 16% in water. The stereochemistry was confirmed by NMR-data and X-ray diffraction. In 0.07 M phosphate buffer at pH 7 and 37 degrees C cis-13 isomerizes to the epimer trans-13, equilibrating at a cis-trans-ratio of 59 to 41 within less than 5 minutes. Simultaneously a rapid initial hydrolysis occurs to 2 and 14 followed by a time period with lower degradation due to the decomposition of 2. The rate of release of 2 increases with decreasing concentration and especially by addition of an oxidant. It could be retarded by addition of the corresponding thiol mesna, sodium 2-mercapto-ethanesulfonate 15, or of another thiol.(ABSTRACT TRUNCATED AT 250 WORDS)

Biotransformation↗