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At least 19 recordsLinked to original sources
PubMed2000

Persistent gestational trophoblastic disease: results of MEA (methotrexate, etoposide and dactinomycin) as first-line chemotherapy in high risk disease and EA (etoposide and dactinomycin) as second-line therapy for low risk disease.

Persistent gestational trophoblastic disease is potentially fatal, but the majority of patients are cured with chemotherapy. Any developments in treatment are therefore being directed towards maintaining efficacy and reducing toxicity. We evaluated efficacy and toxicity of methotrexate, etoposide and dactinomycin (MEA) as first-line therapy for high risk disease and etoposide and dactinomycin (EA) as second-line therapy for methotrexate-refractory low risk disease in a retrospective analysis of 73 patients (38 MEA, 35 EA) treated since 1986 at a supra-regional centre. The median follow-up period was 5.5 years and the median number of cycles received was 7. The overall complete response rate was 85% (97% for EA, 75% for MEA). Of eight patients who failed to respond, four have since died and four were cured with platinum-based chemotherapy. Alopecia was universal. Grade II or worse nausea, emesis, or stomatitis was observed in 29%, 30% and 37% respectively. Fifty-one per cent experienced grade II/III anaemia, 8% grade II or higher thrombocytopenia and 64% grade III or IV neutropenia; in six cases this was complicated by sepsis. Fifty-four per cent of patients went on to have a normal pregnancy. No patient has developed a second malignancy. In conclusion, the MEA and EA chemotherapy regimens for persistent trophoblastic disease are very well tolerated, do not appear to affect future fertility and are associated with excellent, sustained complete response rates.

Adult↗
PubMed1989

A prospective randomized comparison of methotrexate, dactinomycin, and chlorambucil versus methotrexate, dactinomycin, cyclophosphamide, doxorubicin, melphalan, hydroxyurea, and vincristine in "poor prognosis" metastatic gestational trophoblastic disease: a Gynecologic Oncology Group study.

In 1981, the Gynecologic Oncology Group initiated a prospective randomized study in which patients with poor-prognosis gestational trophoblastic disease received either standard MAC chemotherapy (methotrexate, dactinomycin, and chlorambucil) or the modified CHAMOMA regimen (methotrexate, dactinomycin, cyclophosphamide, doxorubicin, melphalan, hydroxyurea, and vincristine). The protocol was closed in May 1986 because the modified CHAMOMA regimen was significantly more toxic and possibly less effective. There were 42 patients entered, with 22 receiving MAC and 20 receiving modified CHAMOMA. There have been six deaths due to disease in the modified CHAMOMA group and none in the MAC group. Five MAC failures and one modified CHAMOMA failure have been rescued by surgery and/or chemotherapy. All six of the patients who died on the modified CHAMOMA regimen had developed disease following a previous term pregnancy, but none had prior chemotherapy. All seven patients who were treated for gestational trophoblastic disease after term pregnancy in the MAC group were cured of disease. With the modified CHAMOMA regimen, 44% of patients had life-threatening hematologic toxicity, as compared with only 9% of the MAC patients. Thus, the standard MAC regimen appears to be at least equally effective and much less toxic than the modified CHAMOMA regimen, indicating a more favorable therapeutic index.

Adult↗
PubMed1980

Treatment of women with disseminated or recurrent advanced ovarian cancer with melphalan alone in combination with 5-fluorouracil and dactinomycin or with the combination of cytoxan, 5-fluorouracil and dactinomycin.

The purpose of this study was to determine the efficacy of single and multiple drug chemotherapeutic regimens in the treatment of patients with advanced or recurrent, Stage III and IV, ovarian epithelial carcinoma. Patients were randomly assigned to one of four treatment regimens postoperatively, or at the time of recurrence: Regimen I--Melphalan (MEL) 0.2 mg/kg/day for five days every four weeks; regimen II--MEL as in Regimen I plus 5-fluorouracil (FU) 15 mg/kg/day for five days every four weeks; regimen III--MEL and FU as in regimen II plus dactinomycin (AC) 0.5 mg daily for five days every four weeks; and regimen IV--Cytoxan (CY) 7 mg/kg/day, FU 8 mg/kg/day and AC 0.5 mg/day for five days every four weeks. Four hundred and twenty-seven patients were in the study, 314 of whom are evaluable for progression-free interval (PFI), survival, and toxicity: 102 in regimen I, 80 in regimen II, 83 in regimen III, and 49 in regimen IV. Of these, 293 were considered evaluable for response. Because of excessive toxicity, entry of patients to regimen IV was discontinued midway through the study. The overall toxicity was quite high but was most severe in regimen II and IV where 16 toxicity deaths were recorded. The complete and partial response rate with Melphalan alone was 29.2%. This response rate was not enhanced by the addition of FU or FU and AC and not substantially different than the response rate of AC, FU, and CY.

Cyclophosphamide↗
PubMed1992

Selective inhibition by dactinomycin of NANC sensory bronchoconstriction and [125I]NKA binding due to NK-2 receptor antagonism.

In the present study, dactinomycin (10(-5) M) inhibited the non-adrenergic, non-cholinergic bronchoconstriction upon antidromic vagal nerve stimulation (1 Hz for 1 min) in the isolated perfused guinea-pig lung by 84%. The release of calcitonin gene-related peptide was unchanged, however, suggesting a postjunctional action. Dactinomycin (10(-5), 5 x 10(-5) M) also reduced non-adrenergic non-cholinergic bronchial contractions (maximally by 75%) induced by electrical field stimulation or capsaicin, while the cholinergic component and non-adrenergic non-cholinergic relaxation remained intact. The neurokinin-2 receptor antagonist L-659,877 (10(-6) M) had a similar effect as dactinomycin, inhibiting the non-adrenergic non-cholinergic bronchial contractions by 69%, while the neurokinin-1 receptor antagonist CP-96,345 (10(-6) M) had no effect. The bronchoconstriction evoked by neurokinin A, the selective neurokinin-2 receptor agonist Nle10neurokinin A (4-10) and capsaicin was markedly inhibited by dactinomycin while the contraction induced by substance P (SP), the selective neurokinin-1 receptor agonist Sar9Met(O2)11SP, endothelin-1 and acetylcholine was not affected. In autoradiographic experiments on guinea-pig lung, [125I]neurokinin A-labelled sections showed dense binding in the bronchial smooth muscle layer. Dactinomycin inhibited the specific binding of [125I]neurokinin A in a concentration-dependent manner (IC50 = 6.3 x 10(-6) M) and 66% of [125I]neurokinin A total binding was inhibited by 10(-4) M dactinomycin. In the rat colon, [125I]neurokinin A binding to neurokinin-2 sites on circular smooth muscle was inhibited by dactinomycin with an IC50 value of 7.9 x 10(-6) M. Dactinomycin failed to reduce increased nerve-evoked contractions or those caused by Nle10neurokinin A (4-10) per se in the rat vas deferens, which are considered to be mediated by neurokinin-2 receptor activation. In the rat portal vein, dactinomycin did not influence the contractions caused by the neurokinin-3 selective agonist Pro7neurokinin B. In conclusion, dactinomycin selectively inhibited neurokinin-2 receptor activation in guinea-pig lung and rat colon, but not in rat vas deferens, which may depend on the existence of different neurokinin-2 receptor subtypes. Neurokinin A is most likely the main endogenous excitatory non-adrenergic non-cholinergic transmitter in guinea-pig bronchi.

Acetylcholine↗
PubMedDate not supplied

Experimental model of hepatic venoocclusive disease (VOD) caused by dactinomycin--preliminary report about hepatoprotective effect of amifostine.

UNLABELLED: The purpose of the study was elaboration of the experimental model of hepatic venoocclusive disease (VOD) induced by dactinomycin and investigation of possible hepatoprotective effects of amifostine and heparin individually or in combination with dexamethasone. 198 Wistar strain male rats were used in the trial in two series of experiments. In the first series the experimental model of VOD induced by dactinomycin was elaborated on the group of 18 animals (divided into 3 groups receiving intraperitoneally isotonic salt solution, dactinomycin or nitrosamine). Nitrosamine--a well-known agent causing VOD--was used as positive control. Open biopsies of the liver and blood collections were repeated in order to determine liver enzymes' concentrations. Histopathological examinations demonstrated that dactinomycin caused liver lesion corresponding with VOD picture. Second series of animals was divided into 6 groups receiving the following drugs: I--0.9% NaCl solution, II--dactinomycin (ACT), III--ACT + fraxiparine s.c., IV--ACT + fraxiparine + dexamethasone, V--ACT + amifostine. Five animals from each group were sacrificed on the 3rd and 7th day after each cycle of drug administration. Blood was drawn in order to determine the following: AspAT, AlAT, Falk, GGTP and LDH. Intravital wedge biopsies under anesthesia with the use of inactin were also performed. Liver samples were stained with the use of H&E, p. a. S and Gomory's techniques. We did not find significant differences in liver enzymes' levels between the groups. Pathological changes corresponding with VOD picture of different intensification were found in liver samples from all the rats receiving ACT. Changes became more and more intensive after consecutive cycles. Lesion of central veins' and liver sinusoids' endothelium dominated. Fraxiparine administered individually or in combination with dexamethasone did not prevent the lesion. Administration of amifostine before ACT decreased pathomorphological changes in liver. Dactinomycin caused homogenous subclinical liver lesion corresponding with VOD. It may also occur in children receiving ACT in the course of nephroblastoma's treatment. But probably the changes are too subtle to manifest themselves clinically with exception of patients particularly sensitive (for example after previous radiotherapy). Lack of differences observed in liver enzymes' levels between the groups supports the explanation. Markers of lesion of liver vessels' endothelium should be looked for to make more specific diagnostics of VOD possible. Hepatoprotective properties of amifostine need further studies. CONCLUSIONS: 1. It is possible to create the experimental model of VOD induced by dactinomycin administration. 2. Amifostine seems to act hepatoprotectively to liver lesions caused by dactinomycin.

Alanine Transaminase↗
PubMed1988

Methotrexate-induced resistance to dactinomycin in choriocarcinoma.

NaUCC-2, a choriocarcinoma cell line, was derived from a patient who had a very poor clinical response to combination chemotherapy. Methotrexate (MTX) might have inhibited the antitumor effect of dactinomycin. To investigate this point, in vitro studies were performed to determine the sensitivity and uptake of MTX and dactinomycin (administered individually and in combination) to NaUCC-2 and three other choriocarcinoma cell lines. Dihydrofolate reductase (DHFR) concentrations were studied as well. Although NaUCC-2 showed sensitivity to MTX and dactinomycin, which were comparable to the other cell lines when they were given separately, NaUCC-2 was unique in that the combination of MTX and dactinomycin was less lethal than dactinomycin given by itself. The uptake of MTX in NaUCC-2 was significantly higher than that in the other cell lines, and MTX also induced an increase in dactinomycin uptake in NaUCC-2. There was no significant difference in DHFR activity. Although additional studies are necessary to determine the mechanism responsible for this effect, these findings suggest that a mechanism other than drug uptake or DHFR activity must play a role in the drug resistance for choriocarcinoma. These findings also suggest that the most commonly used combination chemotherapy for choriocarcinoma, dactinomycin and MTX, may not always be the best method.

Adult↗
PubMed2004

Single-agent pulse dactinomycin has only modest activity for methotrexate-resistant gestational trophoblastic neoplasia.

OBJECTIVES: To determine the effectiveness of single-agent pulse dactinomycin for methotrexate-resistant low-risk gestational trophoblastic neoplasia (GTN). METHODS: Ten patients with low-risk GTN (WHO/FIGO score <8) previously treated with uterine evacuation and single-agent methotrexate were treated with pulse dactinomycin 1.25 mg/m(2) every 2 weeks. RESULTS: Patients had antecedent pregnancies of complete mole (7), partial mole (1), missed abortion (1), and choriocarcinoma (1). One patient underwent hysterectomy during methotrexate treatment. The mean hCG level and WHO score before dactinomycin was 1476 and 4.1, respectively. Six of 10 (60%) patients achieved complete remission with single-agent pulse dactinomycin. Two others responded to a 5-day regimen of dactinomycin, 1 responded to a multidrug regimen, and 1 had chemo-resistant disease dying of metastatic choriocarcinoma. After median follow-up of 11.9 months, 9 of 10 patients remain without relapse. A mean of 3.3 (1-6) cycles were given-4.5 (3-6) for responders and 1.5 (1-2) for nonresponders. In 33 cycles of chemotherapy administered, there were 46 toxicity events: all events were graded as 1. While WHO scores were comparable between responders and nonresponders (mean 3.8 vs. 4.5), hCG levels were lower in responders (mean 37 vs. 3634) but the sample size was too small to reach statistical significance. CONCLUSIONS: Although remission rates of 80-90% have been reported for pulse dactinomycin, patients with methotrexate-resistant GTN had only a 60% remission rate. Prediction of remission may be more closely associated with hCG levels than with WHO score alone.

Adult↗
PubMedDate not supplied

Dactinomycin impairs cellular respiration and reduces accompanying ATP formation.

The effect of dactinomycin on cellular respiration and accompanying ATP formation was investigated in Jurkat and HL-60 cells. Cellular mitochondrial oxygen consumption (measured by a homemade phosphorescence analyzer) and ATP content (measured by the luciferin-luciferase bioluminescence system) were determined as functions of time t during continuous exposure to the drug. The rate of respiration, k, was the negative of the slope of [O2] versus t. Oxygen consumption and ATP content were diminished by cyanide, confirming that both processes involved oxidations in the mitochondrial respiratory chain. In the presence of dactinomycin, k decreased gradually with t, the decrease being more pronounced at higher drug concentrations. Cellular ATP remained constant for 5 h in untreated cells, but in the presence of 20 microM dactinomycin it decreased gradually (to one-tenth the value at 5 h for untreated cells). The drug-induced inhibition of respiration and decrease in ATP were blocked by the pancaspase inhibitor benzyloxycarbonyl-Val-Ala-DL-Asp-fluoromethyl ketone (zVAD-fmk). A rapid but temporary decrease in cellular ATP observed on the addition of zVAD-fmk was shown to be due to DMSO (added with zVAD-fmk). The effect of dactinomycin on respiration differed from that of doxorubicin. Plots of [O2] versus t were curved for dactinomycin so that k decreased gradually with t. The corresponding plots for doxorubicin were well fit by two straight lines; so k was constant for approximately 150 min, at which time k decreased, remaining constant at a lower level thereafter. The results for cells treated with mixtures of the two drugs indicated that the drugs acted synergistically. These results show the onset and severity of mitochondrial dysfunction in cells undergoing apoptosis induced by dactinomycin.

Adenosine Triphosphate↗
PubMed1993

Dactinomycin analogues as neurokinin-2 receptor antagonists.

Dactinomycin has recently been shown to be a competitive neurokinin-2 receptor antagonist in addition to its inhibiting action on DNA replication. We investigated in the isolated guinea-pig bronchi the action of 3 Dactinomycin analogues on the contractions evoked by the selective neurokinin-2 receptor agonist [Nle10] neurokinin A(4-10). These analogues included 4,4'-Gly-Dactinomycin and the single peptide lactone of dactinomycin which are inactive on DNA replication and 5,5'-MeLeu-Dactinomycin, which has potent antitumour activity. Independently of their known effect on DNA replication, the three analogues showed neurokinin-2 antagonistic activity which was lower than for Dactinomycin.

Animals↗
PubMed2005

Pharmacokinetics of dactinomycin in a pediatric patient population: a United Kingdom Children's Cancer Study Group Study.

PURPOSE: Dactinomycin (actinomycin D) is an antitumor antibiotic used routinely to treat certain pediatric and adult cancers. Despite concerns over the incidence of toxicity, little is known about the pharmacology of dactinomycin. A study was done to investigate dactinomycin pharmacokinetics in children. EXPERIMENTAL DESIGN: Dactinomycin was administered to 31 patients by bolus i.v. infusion, at doses of 0.70 to 1.50 mg/m2. Plasma concentrations were determined by liquid chromatography-mass spectrometry up to 24 hours after drug administration and National Cancer Institute Common Toxicity Criteria was assessed. RESULTS: Pharmacokinetic data analysis suggested that a three-compartment model most accurately reflected dactinomycin pharmacokinetics. However, there was insufficient data available to fully characterize this model. A median peak plasma concentration (Cmax) of 25.1 ng/mL (range, 3.2-99.2 ng/mL) was observed at 15 minutes after administration. The median exposure (AUC0-6), determined in 16 patients with sampling to 6 hours, was 2.67 mg/L.min (range, 1.12-4.90 mg/L.min). After adjusting for body size, AUC0-6 and Cmax were positively related to dose (P = 0.03 and P = 0.04, respectively). Patients who experienced any level of Common Toxicity Criteria grade had a 1.46-fold higher AUC0-6, 95% confidence interval (1.02-2.09). AUC0-6 was higher in patients <40 kg, possibly indicating a greater toxicity risk. CONCLUSIONS: Data presented suggest that dosing of dactinomycin based on surface area is not optimal, either in younger patients in whom the risk of toxicity is greater, or in older patients where doses are capped.

Adolescent↗
PubMed1998

Randomized controlled trial of doxorubicin versus dactinomycin in a multiagent protocol for treatment of dogs with malignant lymphoma.

OBJECTIVE: To compare efficacy and toxicity of 2 multiagent chemotherapeutic protocols similar in all respects except that 1 incorporated dactinomycin and the other incorporated doxorubicin for treatment of dogs with malignant lymphoma. DESIGN: Randomized controlled trial. ANIMALS: 45 dogs with malignant lymphoma. PROCEDURE: Dogs were randomly assigned to a doxorubicin or dactinomycin treatment group. Time to first remission, duration of first remission, survival time, and prevalence of toxicoses, particularly number of episodes of dose-limiting neutropenia and gastrointestinal toxicoses, were compared between groups. RESULTS: 37 dogs received at least 1 dose of doxorubicin (21 dogs) or dactinomycin (16). Median time to first remission was not significantly different between groups, but median duration of first remission and median survival time were significantly longer for dogs in the doxorubicin treatment group than for dogs in the dactinomycin treatment group. Number of dogs that died, number of episodes of dose-limiting neutropenia, and number of episodes of gastrointestinal toxicoses were not significantly different between groups. CLINICAL IMPLICATIONS: A multiagent chemotherapeutic protocol incorporating doxorubicin was significantly more effective in dogs with malignant lymphoma than a similar protocol incorporating dactinomycin. Despite the lower cost and lack of cardiotoxicity, dactinomycin is not an equivalent substitute for doxorubicin in the initial treatment of dogs with malignant lymphoma.

Animals↗
PubMed1985

Extravasation of dactinomycin, vincristine, and cisplatin: studies in an animal model.

Extravasation of some cytotoxic drugs results in chemical cellulitis. Management of suspected extravasation has been empiric and difficult to evaluate clinically. We investigated dactinomycin, vincristine, and cisplatin by means of intradermal injections in Balb-c mice. Reproducible skin lesions with concentric areas of induration, erythema, and ulceration developed in a time- and dose-dependent fashion following injection of dactinomycin. Vincristine caused no lesions following initial intradermal administration, but repeat injection 7 days later was followed by a diffuse punctate ulcerative lesion suggesting a hypersensitivity reaction. Three concentrations (1.0, 0.1, and 0.01 mg/ml) of cisplatin elicited cellulitis following initial injection, but there was no correlation between lesion size and dose. Injection of saline, hydrocortisone, ascorbic acid, sodium thiosulfate, buffered DNA solution, and beta adrenergic agonists and antagonists after the injection of dactinomycin failed to prevent development of lesions. Heat application was also ineffective; however, local cold application prevented or markedly reduced reactions to dactinomycin. We conclude that the intradermal mouse model may be appropriate for the evaluation of the three drugs studied and that cold application is the best antidote among those tested for dactinomycin-induced ulceration in this model.

Adrenal Cortex Hormones↗
PubMed1991

Dactinomycin is a competitive neurokinin-2 receptor antagonist.

Dactinomycin, a peptide antibiotic from Streptomyces spp., is a classical agent which inhibits DNA replication. In the present study, dactinomycin inhibited specific [125I]NKA binding in rat colon membranes (KI = 1.05 x 10(-5) M) in a competitive manner. Furthermore, dactinomycin caused a parallel rightward shift of the concentration-response curve for the contractions in the rat colon induced by the NK-2 receptor agonist [Nle10]-NKA(4-10). A selective inhibition of NK-2 receptors by dactinomycin was supported by the absence of inhibition of NK-1 receptors activation in guinea pig vas deferens and of NK-3 receptors in rat portal vein. The structural similarity of the cyclic peptide moieties of dactinomycin to L-659,877, a known NK-2 receptor antagonist, can probably account for the present observations.

Amino Acid Sequence↗
PubMedDate not supplied

Dactinomycin potentiation of radiation pneumonitis: a forgotten interaction.

No mention of dactinomycin potentiation of pulmonary radiation was found in a review of the literature of the past 12 years. Before that, this complication was well described and investigators had calculated that dactinomycin increased the toxic effect of lung radiation by a factor of 1.3 and reduced the radiation tolerance of the lung by at least 20%. An example of such a toxic effect is described in the treatment of a 7-year-old girl with lung metastases from Ewing's sarcoma. The chemotherapy protocol followed contained cyclophosphamide, vincristine, dactinomycin, adriamycin, cisplatinum, VP16, and radiotherapy. The treatment was associated with fatal pulmonary fibrosis following the reintroduction of dactinomycin after radiotherapy. Our experience suggests that there is clinical significance to this complication in sarcoma therapy when dactinomycin-containing protocols are used with radiation in the treatment of pulmonary metastases.

Animals↗
PubMed2000

[The effect of dactinomycin on retinal injury induced by argon laser in mouse].

OBJECTIVE: To determine that the administration of RNA synthesis inhibitor (dactinomycin) prevents retinal photoreceptor cell injury induced by green wavelength of argon laser in SD mice. METHODS: At various time (0, 8, 20 h) after the exposure to laser, eyes of the mice were injected intraocularly with dactinomycin in experimental eyes, and saline in control ones, and the concentration of the drug were 10 g/L, 5 g/L, 2.5 g/L. The eyes were taken at 24 h after the exposure, the slices of the retina were stained with methyl green-pyronin (MG-P), and pyknotic (violet) as well as surviving cells (green) were counted in the laser burns. RESULTS: Intraocular administration of dactinomycin diminished the degeneration induced by argon laser, there were marked differences between the experimental group and the control group, dactinomycin showed to be more effective if administered immediately after exposure and 8 h later, after this time the higher concentration of the drug could not result in higher effect. CONCLUSION: Dactinomycin can inhibit the occurrence of the laser injury, but the time selected for the administration is critical for its efficacy.

Animals↗
PubMed1988

Severe hepatic toxicity after treatment with single-dose dactinomycin and vincristine. A report of the National Wilms' Tumor Study.

Dactinomycin is an antitumor antibiotic with known activity against many pediatric solid tumors. Administration of dactinomycin using a single-dose schedule was incorporated into the design of the National Wilms' Tumor Study 4 (NWTS-4). This was done to determine whether laboratory and preliminary clinical data, suggesting that such a schedule was associated with increased antitumor effect and/or decreased normal tissue toxicity, could be validated in a large clinical trial. Five patients treated with regimens EE-4 or K-4, regimens that included single-dose dactinomycin and no abdominal irradiation, experienced severe hepatic toxicity. The clinical courses of these patients suggested that multiple factors, including the administration of other hepatotoxic agents, contributed to the toxicity observed. The study has been modified by decreasing the dose of dactinomycin from 60 micrograms/kg to 45 micrograms/kg. Further evaluation of other potential contributing factors, such as the use of halogenated hydrocarbon inhalational anesthetic agents, is needed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Severe acne and hyperandrogenemia following dactinomycin.

The etiology of dactinomycin-associated acne has not previously been studied. An 81/2 year old girl with embryonal rhabdomyosarcoma of the left petrous bone was prepubertal at the time of presentation. Treatment according to a current Intergroup Rhabdomyosarcoma Study regimen consisted of vincristine, dactinomycin, and cyclophosphamide at 3 to 6 week intervals, as well as hyperfractionated radiotherapy to the tumor bad. Severe acne of the forehead developed within 10 days of starting therapy and resolved over the next 2 months. Serial measurements of serum hormones documented periodic increases in androgen levels coincident with courses of dactinomycin. These observations support a relationship between drug, dermatitis, and hormone levels. Study of other patients will be of interest to document the frequency, degree, and mechanism of hyperandrogenemia following dactinomycin.

Acne Vulgaris↗
PubMed1999

Dactinomycin in the treatment of recurrent or persistent endometrial carcinoma: A Phase II study of the Gynecologic Oncology Group.

OBJECTIVES: The search for effective systemic chemotherapy for endometrial cancer is ongoing. Complete responses to current drugs or regimens are infrequent, and overall survival for patients with disease not amenable to surgery or radiation therapy is poor. Dactinomycin has proven activity against a wide variety of solid tumors but has not been tested against endometrial cancer. Using pharmacokinetic data supporting an intermittent, single-dose schedule, this Phase II Gynecologic Oncology Group study was conducted to determine the antitumor activity and toxicity of dactinomycin in patients with persistent or recurrent endometrial adenocarcinoma. METHODS: Eligibility was limited to patients with measurable disease, adequate renal, hepatic, and bone marrow function, and no more than one prior chemotherapy regimen. Treatment consisted of 2 mg/m(2) slow intravenous push of dactinomycin over 15 min with courses repeated every 4 weeks. RESULTS: A total of 27 patients were entered in this study between April 1996 and September 1996; all were evaluable for toxicity and 25 were evaluable for response. Overall, 12/25 (48%) patients had received prior radiation therapy and all had received prior chemotherapy. Sites of measurable disease were pelvis (9 patients) and distant (16 patients). There was 1 complete response and 2 partial responses for an overall objective response rate of 12%. Aside from emesis (grade 3, 2 patients; grade 4, 2 patients) significant nonhematologic toxicity was rare. The most common toxicity was neutropenia (grade 3, 2 patients; grade 4, 10 patients). CONCLUSION: Toxicity was deemed acceptable but the limited effectiveness of dactinomycin precludes further clinical development in this patient population.

Adult↗