"A compound composed of a two CYCLIC PEPTIDES attached to a phenoxazine that is derived from STREPTOMYCES parvullus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy. (From AMA Drug Evaluations Annual, 1993, p2015)" (MeSH 2013)
Latest Research Publications
Web Resources: Dactinomycin (6 links)
This list of publications is regularly updated (Source: PubMed).
Treatment Outcomes of Gestational Trophoblastic Neoplasia in King Chulalongkorn Memorial Hospital over Two Decades.
J Reprod Med. 2016 May-Jun; 61(5-6):238-42 [PubMed] Related Publications
STUDY DESIGN: This retrospective study recruited all GTN patients who were treated at King Chulalongkorn Memorial Hospital during the period January 1994-December 2013. Clinical data were collected. Statistical analyses were performed, with p values < 0.05 considered statistically significant.
RESULTS: There were 183 GTN cases during the study period, resulting in an incidence of 1.03 cases per 1,000 deliveries. Fifty-five cases (30.1%) were diagnosed as GTN following nonmolar pregnancy, and 128 cases were identified as postmolar GTN. A total of 113 cases were diagnosed as stage I, 12 as stage II, 40 as stage III, and 17 as stage IV; 125 cases (68.3%) were clas- sified as low risk, and 57 cases (31.1%) as high risk. Actinomycin D was the most frequently used first-line single-agent chemotherapy (98 cases), and VAC regimen was the most frequently used combination chemotherapy (24 cases). EMACO regimen was the most frequently used second-line chemotherapy (11 cases). The median number of chemotherapy courses was 4.5 courses in the first decade and 6 courses in the second decade of our study (p = 0.005). Median duration of treatment was 72 days (range, 7-491 days). Overall remission rate was 82.6%, with rates of 76% in the first decade and 90.8% in the second decade of the study (p=0.03).
CONCLUSION: Incidence of high-risk GTN increased over the course of the study period at our national referral hospital. Improvement in patient outcomes was observed, being directly associated with improved targeted chemotherapy regimens.
Comparison of Cost-Effectiveness Between Actinomycin D Versus Methotrexate-Folinic Acid in the Treatment of Low-Risk Gestational Trophoblastic Neoplasia.
J Reprod Med. 2016 May-Jun; 61(5-6):230-4 [PubMed] Related Publications
STUDY DESIGN: A comparative cost-effectiveness analysis was performed from a societal perspective. A decision tree model was developed comparing 2 alternative treatment options: initial 5-day Act-D and 8-day MTX-FA. Treatment would be switched to another regimen in case of resistance. The outcome of interest is number of days to remission. Clinical data was obtained from our previous study in which Act-D demonstrated 100% remission rates as compared to 73.6% for MTX-FA. Cost of treatment data, which includes chemotherapeutics, accessory medications, laboratory tests, and hospital fees, was obtained from a university hospital. Patient-related travel cost and opportunity cost due to absence from work were also included. All costs were calculated to 2015 base year.
RESULT: Costs per treatment cycle were $308.01 and $227.20 US dollars (USD) for 5-day Act-D and 8-day MTX-FA, respectively. Expected time toward treatment completion for Act-D was 12.6 days shorter than for MTX-FA. Expected costs toward remission for initial treatment with Act-D and MTX-FA were $1,078.04 and $1,064.56 USD, respectively, i.e., an incremental cost effectiveness ratio (ICER) of $1.07 USD/day of earlier treatment completion. After sensitivity analysis, remission rate of lower than 72% would make initial treatment with MTX-FA more expensive than with Act-D.
CONCLUSION: Treatment costs of low-risk GTN are almost equal between the 2 treatment options with different time to remission. Initial treatment with MTX-FA is slightly less expensive, but there is longer time to remission. The ICER of initial treatment with Act-D over MTX-FA is $1.07 USD/day of earlier treatment completion.
First-line chemotherapy in low-risk gestational trophoblastic neoplasia.
Cochrane Database Syst Rev. 2016; (6):CD007102 [PubMed] Related Publications
OBJECTIVES: To determine the efficacy and safety of first-line chemotherapy in the treatment of low-risk GTN.
SEARCH METHODS: We electronically searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase in September 2008, February 2012, and January 2016. In addition, we searched online trial registers for protocols and ongoing trials.
SELECTION CRITERIA: For the original review, we included randomised controlled trials (RCTs), quasi-RCTs and non-RCTs that compared first-line chemotherapy for the treatment of low-risk GTN. For this updated versions of the review, we included only RCTs.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion and extracted data to a pre-designed data extraction form. Meta-analysis was performed using the random-effects model.
MAIN RESULTS: We included seven RCTs (667 women) in this updated review. Most studies were at a low or moderate risk of bias and all compared methotrexate with actinomycin D. Three studies compared weekly intramuscular (IM) methotrexate with bi-weekly pulsed intravenous (IV) actinomycin D (393 women), one study compared five-day IM methotrexate with bi-weekly pulsed IV actinomycin D (75 women), one study compared eight-day IM methotrexate-folinic acid (MTX-FA) with five-day IV actinomycin D (49 women), and one study compared eight-day IM MTX-FA with bi-weekly pulsed IV actinomycin D. One study contributed no data. Moderate-certainty evidence indicates that actinomycin D is probably more likely to lead to primary cure than methotrexate (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.57 to 0.75; six trials, 577 participants; I(2) = 26%), and first-line methotrexate treatment is probably more likely to fail than actinomycin D treatment (RR 3.55, 95% CI 1.81 to 6.95; six trials, 577 participants; I(2) = 61%; moderate-certainty evidence) Low-certainty evidence suggests that there may be little or no difference between methotrexate and actinomycin D treatment with respect to nausea (four studies, 466 women; RR 0.61, 95% CI 0.29 to 1.26) or any of the other individual side-effects reported, although data for all of these outcomes were insufficient and too inconsistent to be conclusive. Low-certainty evidence suggests that there may be little or no difference in the risk of severe adverse events (SAEs) between the groups overall (five studies, 515 women; RR 0.35, 95% CI 0.08 to 1.66; I² = 60%); however, the direction of effect favours methotrexate and more evidence is needed. Furthermore, evidence from subgroup analyses suggests that actinomycin D may be associated with a greater risk of SAEs than methotrexate (low-certainty evidence). We found no evidence on the effect of these treatments on future fertility.
AUTHORS' CONCLUSIONS: Actinomycin D is probably more likely to achieve a primary cure in women with low-risk GTN, and less likely to result in treatment failure, than a methotrexate regimen. There may be little or no difference between the pulsed actinomycin D regimen and the methotrexate regimen with regard to side-effects. However, actinomycin D may be associated with a greater risk of severe adverse events (SAEs) than a methotrexate regimen. Higher-certainty evidence is still needed on treating low-risk GTN and the four ongoing trials are likely to make a significant contribution to this field. Given the variety of treatment regimens, findings from these trials could facilitate a network meta-analysis in the next version of this review to help women and clinicians determine the best treatment options for low-risk GTN.
Methotrexate and actinomycin D chemotherapy in a patient with porphyria: a case report.
J Med Case Rep. 2016; 10:9 [PubMed] Free Access to Full Article Related Publications
CASE PRESENTATION: In this report, we present a case of an invasive mole with lung metastasis in a 49-year-old Japanese woman who had previously been diagnosed with acute intermittent porphyria at 27 years of age but had no recent history of acute intermittent porphyria attacks. Her serum human chorionic gonadotropin level was elevated 1 month after hysterectomy, and she was referred to our center for chemotherapy. After she received 100 mg of methotrexate, drug eruptions were observed starting on day 3 and grew progressively worse. Erythema and mucosal erosion spread throughout her body, whereupon she was administered prednisolone. In addition, our patient experienced febrile neutropenia and required granulocyte colony- stimulating factor treatment. No changes in our patient's urinary coproporphyrin or uroporphyrin levels were detected during this entire episode. Methotrexate was replaced by actinomycin D (0.5 mg/body intravenously on days 1-5 every 2 weeks). After five uneventful cycles of actinomycin D, our patient achieved and maintained a normal serum human chorionic gonadotropin level for 3 years.
CONCLUSIONS: Methotrexate and actinomycin D did not induce acute porphyric attacks in this patient with acute intermittent porphyria; however, severe adverse effects were noted with methotrexate. Although further investigation is required, our data suggest that these agents are nonporphyrinogenic and can therefore be used to treat patients with comorbid porphyria.
Development of a physiologically based pharmacokinetic model of actinomycin D in children with cancer.
Br J Clin Pharmacol. 2016; 81(5):989-98 [PubMed] Free Access to Full Article Related Publications
METHODS: Assays to determine actinomycin D Log P, blood:plasma partition ratio and ABCB1 kinetics were conducted. These data were combined with physiochemical properties sourced from the literature to generate a compound file for use within the modelling-simulation software Simcyp (version 14 release 1). For simulation, information was taken from two datasets, one from 117 patients under the age of 21 and one from 20 patients aged 16-48.
RESULTS: The final model incorporated clinical renal and biliary clearance data and an additional systemic clearance value. The mean AUC0-26h of simulated subjects was within 1.25-fold of the observed AUC0-26h (84 ng h ml(-1) simulated vs. 93 ng h ml(-1) observed). For the younger age ranges, AUC predictions were within two-fold of observed values, with simulated data from six of the eight age/dose ranges falling within 15% of observed data. Simulated values for actinomycin D AUC0-26h and clearance in infants aged 0-12 months ranged from 104 to 115 ng h ml(-1) and 3.5-3.8 l h(-1) , respectively.
CONCLUSIONS: The model has potential utility for prediction of actinomycin D exposure in younger patients and may help guide future dosing. However, additional independent data from neonates and infants is needed for further validation. Physiological differences between paediatric cancer patients and healthy children also need to be further characterized and incorporated into PBPK models.
Apoptosis of human prostate cancer cells induced by marine actinomycin X2 through the mTOR pathway compounded by MiRNA144.
Anticancer Drugs. 2016; 27(3):156-63 [PubMed] Related Publications
Tegafur Substitution for 5-Fu in Combination with Actinomycin D to Treat Gestational Trophoblastic Neoplasm.
PLoS One. 2015; 10(11):e0143531 [PubMed] Free Access to Full Article Related Publications
Validation of the Predictive Value of Modeled Human Chorionic Gonadotrophin Residual Production in Low-Risk Gestational Trophoblastic Neoplasia Patients Treated in NRG Oncology/Gynecologic Oncology Group-174 Phase III Trial.
Int J Gynecol Cancer. 2016; 26(1):208-15 [PubMed] Related Publications
METHODS: Database (210 patients, including 78 with resistance) was split into 2 sets. A 126-patient training set was initially used to estimate model parameters. Patient hCG kinetics from days 7 to 45 were fit to: [hCG(time)] = hCG7 * exp(-k * time) + hCGres, where hCGres is residual hCG tumor production, hCG7 is the initial hCG level, and k is the elimination rate constant. Receiver operating characteristic (ROC) analyses defined putative hCGRes predictor of resistance. An 84-patient test set was used to assess prediction validity.
RESULTS: The hCGres was predictive of outcome in both arms, with no impact of treatment arm on unexplained variability of kinetic parameter estimates. The best hCGres cutoffs to discriminate resistant versus sensitive patients were 7.7 and 74.0 IU/L in arms 1 and 2, respectively. By combining them, 2 predictive groups were defined (ROC area under the curve, 0.82; sensitivity, 93.8%; specificity, 70.5%). The predictive value of hCGres-based groups regarding resistance was reproducible in test set (ROC area under the curve, 0.81; sensitivity, 88.9%; specificity, 73.1%). Both hCGres and treatment arm were associated with resistance by logistic regression analysis.
CONCLUSIONS: The early predictive value of the modeled kinetic parameter hCGres regarding resistance seems promising in the GOG-174 study. This is the second positive evaluation of this approach. Prospective validation is warranted.
Low-Dose Actinomycin-D Induces Redistribution of Wild-Type and Mutated Nucleophosmin Followed by Cell Death in Leukemic Cells.
J Cell Biochem. 2016; 117(6):1319-29 [PubMed] Related Publications
Actinomycin D and nutlin-3a synergistically promote phosphorylation of p53 on serine 46 in cancer cell lines of different origin.
Cell Signal. 2015; 27(9):1677-87 [PubMed] Related Publications
Burden of disease predicts response to isolated limb infusion with melphalan and actinomycin D in melanoma.
Ann Surg Oncol. 2015; 22(2):482-8 [PubMed] Free Access to Full Article Related Publications
METHODS: We retrospectively analyzed a prospectively collected database from two academic centers. BOD was stratified as high or low (low ≤ 10 lesions, none >2 cm). Response rates were measured 3 months post-ILI. Multivariable analysis (MV) was used to evaluate the association between the response and BOD. Kaplan-Meier methods with log-rank tests and MV Cox proportional hazard models were used to analyze overall survival (OS) and progression free survival (PFS).
RESULTS: Sixty (38 %) patients had low and 100 (62 %) high BOD. Patients with low BOD had an overall response rate (ORR) of 73 % with 50 % CR, compared with an ORR of 47 % with 24 % CR in patients with high BOD (p = 0.002). MV analysis of preoperative, intraoperative, and postoperative parameters showed no significant impact on 3-month response. Patients with a CR at 3 months demonstrated improved PFS over the remainder of the cohort, but OS was similar. Low BOD patients had an increased median PFS of 6.9 versus 3.8 months (p = 0.047) and a increased median OS of 38.4 versus 30.9 months (p = 0.146).
CONCLUSIONS: Lower BOD is associated with an increased ORR and CR rate with statistically significantly improved PFS in patients undergoing ILI for in transit extremity melanoma. BOD provides useful prognostic information for patient counseling and serves as a marker to stratify patient risk groups.
Characterisation of the clinical pharmacokinetics of actinomycin D and the influence of ABCB1 pharmacogenetic variation on actinomycin D disposition in children with cancer.
Clin Pharmacokinet. 2014; 53(8):741-51 [PubMed] Free Access to Full Article Related Publications
METHODS: A total of 650 plasma samples collected over an 8 year period from 117 patients ≤21 years receiving Act D (0.4-1.6 mg/m(2)) were used to characterise a population pharmacokinetic model. Polymorphisms in ABCB1 were analysed in 140 patients.
RESULTS: A 3-compartment model provided a good fit to the data. Median values for Act D clearance and volume of distribution in the central compartment (V 1) obtained from the model were 5.3 L/h and 1.9 L (13.9 L/h/70 kg and 7.5 L/70 kg), respectively. There was substantial inter-subject variation in all pharmacokinetic parameters (coefficients of variation 53-81 % for non-normalised values). Body weight was a major determinant of Act D clearance, such that dose capping at 2 mg in larger children at a protocol dose of 1.5 mg/m(2) resulted in significantly lower area under the plasma concentration-time curves (mean AUC values: 9.3 versus 12.8 mg·min/L; P < 0.0001). No significant relationships were found between ABCB1 genetic variants and Act D pharmacokinetic parameters, nor between CL, V 1 or dose and incidence of grade 3 or 4 toxicity.
CONCLUSION: We have defined the pharmacokinetics of Act D in a paediatric patient population, providing robust estimates of key pharmacokinetic parameters. Pharmacokinetic data bring into question the current clinical practice of dose capping at 2 mg in larger patients. Pharmacogenetic variation in candidate drug transporter genes identified from preclinical studies does not significantly impact on Act D exposure in a clinical setting.
Rapamycin prevents strong phosphorylation of p53 on serine 46 and attenuates activation of the p53 pathway in A549 lung cancer cells exposed to actinomycin D.
Mech Ageing Dev. 2014; 139:11-21 [PubMed] Related Publications
Hepatopathy-Thrombocytopenia Syndrome During Actinomycin D Treatment May Be Related to MDR1 (ABCB1) Gene Polymorphisms.
Am J Ther. 2016 Mar-Apr; 23(2):e594-6 [PubMed] Related Publications
p53-Based cyclotherapy: exploiting the 'guardian of the genome' to protect normal cells from cytotoxic therapy.
Br J Cancer. 2013; 109(12):2954-8 [PubMed] Free Access to Full Article Related Publications
Hepatopathy-thrombocytopenia syndrome after actinomycin-D therapy: treatment with defibrotide.
Pediatr Hematol Oncol. 2013; 30(1):25-7 [PubMed] Related Publications
Spermine attenuates the action of the DNA intercalator, actinomycin D, on DNA binding and the inhibition of transcription and DNA replication.
PLoS One. 2012; 7(11):e47101 [PubMed] Free Access to Full Article Related Publications
Prophylactic chemotherapy for hydatidiform mole to prevent gestational trophoblastic neoplasia.
Cochrane Database Syst Rev. 2012; 10:CD007289 [PubMed] Related Publications
OBJECTIVES: To systematically review the evidence for the effectiveness and safety of P-Chem to prevent GTN in women with a molar pregnancy.
SEARCH METHODS: We performed electronic searches in the Cochrane Gynaecological Cancer Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2, 2012), MEDLINE (1946 to February week 4, 2012) and EMBASE (1980 to week 9, 2012). The search strategy was developed using free text and medical subject headings (MESH). We handsearched reference lists of relevant literature to identify additional studies.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) of P-Chem for HM.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion in the review and extracted data using a specifically designed data collection form. Meta-analyses were performed by pooling data from individual trials using RevMan 5.1 software.
MAIN RESULTS: We included three RCTs with a combined total of 613 participants. One study compared prophylactic dactinomycin to no prophylaxis (60 participants); the other two studies compared prophylactic methotrexate to no prophylaxis (420 and 133 participants). All participants were diagnosed with CMs. We considered the latter two studies to be of poor methodological quality.P-Chem reduced the risk of GTN occurring in women following a CM (3 studies, 550 participants; RR 0.37; 95% confidence interval (CI) 0.24 to 0.57; I(2) = 0%; P < 0.00001), However, owing to the poor quality of two of the included studies, we performed sensitivity analyses excluding these two studies. This left only one small study of high-risk women to contribute data for this primary outcome (59 participants; RR 0.28; 95% CI 0.10 to 0.73; P = 0.01), therefore we consider this evidence to be of a low quality.The time to diagnosis was longer in the P-Chem group than the control group (2 studies, 33 participants; mean difference (MD) 28.72; 95% CI 13.19 to 44.24; P = 0.0003) and the P-Chem group required more courses to cure subsequent GTN (1 poor-quality study, 14 participants; MD 1.10; 95% CI 0.52 to 1.68; P = 0.0002). We consider this evidence to be of a low to very low quality for similar reasons to those listed above.There were insufficient data to perform meta-analyses for toxicity, overall survival, drug resistance and reproductive outcomes.
AUTHORS' CONCLUSIONS: P-Chem may reduce the risk of progression to GTN in women with CMs who are at a high risk of malignant transformation; however, current evidence in favour of P-Chem is limited by the poor methodological quality and small size of the included studies. As P-Chem may increase drug resistance, delay treatment of GTN and expose women unnecessarily to toxic side effects, this practice cannot currently be recommended.
Comparison of methotrexate, actinomycin D, and etoposide for treating low-risk gestational trophoblastic neoplasia.
Int J Gynaecol Obstet. 2012; 119(1):35-8 [PubMed] Related Publications
METHODS: A prospective study was conducted at a referral center in Rio de Janeiro, Brazil. Patients presenting with metastatic or non-metastatic LRGTN (risk score ≤ 6) in non-probabilistic sampling were assigned to 1 of 3 treatments: methotrexate with folinic acid rescue (MTX-CF; n=20); actinomycin D (n=20); and etoposide (n=20). Women with less than 1 year of disease-free follow-up after the first normal human chorionic gonadotropin (hCG) value were excluded. Outcome measures included primary remission rate; resistance to primary and sequential chemotherapy; period between treatment initiation and remission (hCG response); and prevalence of toxic effects.
RESULTS: Primary remission was achieved by 48 patients (80.0%). The remission rate with etoposide was 100.0%, while the rates with actinomycin D and MTX-CF were 90.0% and 50.0%, respectively. Efficacy of etoposide was significantly greater than the other 2 agents (P<0.001). Alopecia was the most frequent adverse effect caused by etoposide. Common to all protocols were stomatitis, nausea, and vomiting. Mean time intervals between beginning treatment and remission were similar and all 60 participants survived.
CONCLUSION: Etoposide was the most effective regimen for treating metastatic and non-metastatic LRGTN.
Actinomycin D for methotrexate-failed low-risk gestational trophoblastic neoplasia.
J Reprod Med. 2012 Jul-Aug; 57(7-8):283-7 [PubMed] Related Publications
STUDY DESIGN: We reviewed the records of 358 patients treated with methotrexate 0.4 mg/kg (max 25 mg) IV push q.d. x 5 d every 14 d for FIGO-defined, low-risk GTN between 1979 and 2009. Actinomycin D 0.5 mg IV push q.d. x 5 d every 14 d was given to 64 of 68 patients (18%) who failed methotrexate: 48 (75%) for resistance and 16 (25%) for toxicity. Adjuvant surgery was used in selected patients. Clinical response and survival as well as factors affecting outcomes were analyzed retrospectively.
RESULTS: The complete response rate to secondary chemotherapy with actinomycin D for failed methotrexate treatment of low-risk GTN was 75% (48/64), including 71% (34/48) for methotrexate resistance and 88% (14/16) for methotrexate toxicity. All 20 patients (6%) who failed sequential single-agent chemotherapy with methotrexate and actinomycin D were placed into permanent remission with the use of multiagent chemotherapy with or without surgery. The only factor significantly associated with resistance to secondary actinomycin D chemotherapy was clinicopathologic diagnosis of choriocarcinoma versus postmolar GTN (56% versus 20%, p = 0.025).
CONCLUSION: Actinomycin D 0.5 mg IV q.d. x 5 d every 14 d used as secondary therapy in methotrexate-failed low-risk GTN resulted in a 75% complete response rate and eventual 100% cure with subsequent multiagent chemotherapy with or without surgery. Resistance to sequential methotrexate and actinomycin D chemotherapy was significantly associated with original FIGO score > or = 3 and clinicopathologic diagnosis of choriocarcinoma.
First-line chemotherapy in low-risk gestational trophoblastic neoplasia.
Cochrane Database Syst Rev. 2012; (7):CD007102 [PubMed] Free Access to Full Article Related Publications
OBJECTIVES: To determine the efficacy and safety of first-line chemotherapy in the treatment of low-risk GTN.
SEARCH METHODS: In September 2008, we electronically searched the Cochrane Gynaecological Cancer Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL Issue 3, 2008), MEDLINE and EMBASE. In addition, we searched online trial registers, conference proceedings and reference lists of identified studies. We re-ran these searches in February 2012 for this updated review.
SELECTION CRITERIA: For the original review, we included randomised controlled trials (RCTs), quasi-RCTs and non-RCTs that compared first-line chemotherapy for the treatment of low-risk GTN. For this updated version of the review, we included only RCTs.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion and extracted data to a pre-designed data extraction form. Meta-analysis was performed by pooling the risk ratio (RR) of individual trials.
MAIN RESULTS: We included five moderate to high quality RCTs (517 women) in the updated review. These studies all compared methotrexate with dactinomycin. Three studies compared weekly intramuscular (IM) methotrexate with bi-weekly pulsed intravenous (IV) dactinomycin (393 women), one study compared five-day IM methotrexate with bi-weekly pulsed IV dactinomycin (75 women) and one study compared eight-day IM methotrexate-folinic acid (MTX-FA) with five-day IV dactinomycin (49 women).Overall, dactinomycin was associated with significantly higher rates of primary cure than methotrexate (five studies, 513 women; RR 0.64, 95% Confidence Interval (CI) 0.54 to 0.76). Methotrexate was associated with significantly more treatment failure than dactinomycin (five studies, 513 women; RR 3.81, 95% CI 1.64 to 8.86). We consider this evidence to be of a moderate quality.There was no significant difference between the two groups with respect to nausea (four studies, 466 women; RR 0.61, 95% CI 0.29 to 1.26) or any of the other individual side-effects reported, although data for all of these outcomes were insufficient and too heterogeneous to be conclusive. No severe adverse effects (SAEs) occurred in either group in three out of the five included studies and there was no significant difference in SAEs between the groups overall (five studies, 515 women; RR 0.35, 95% CI 0.08 to 1.66; I² = 60%), however, there was a trend towards fewer SAEs in the methotrexate group. We considered this evidence to be of a low quality due to substantial heterogeneity and low consistency in the occurrence/reporting of SAEs between trials.
AUTHORS' CONCLUSIONS: Dactinomycin is more likely to achieve a primary cure in women with low-risk GTN, and less likely to result in treatment failure, compared with methotrexate. There is limited evidence relating to side-effects, however, the pulsed dactinomycin regimen does not appear to be associated with significantly more side-effects than the low-dose methotrexate regimen and therefore should compare favourably to the five- and eight-day methotrexate regimens in this regard.We consider pulsed dactinomycin to have a better cure rate than, and a side-effect profile at least equivalent to, methotrexate when used for first-line treatment of low-risk GTN. Data from a large ongoing trial of pulsed dactinomycin compared with five- and eight-day methotrexate regimens is likely to have an important impact on our confidence in these findings.
Actinomycin D induces p53-independent cell death and prolongs survival in high-risk chronic lymphocytic leukemia.
Leukemia. 2012; 26(12):2508-16 [PubMed] Related Publications
Modeling and simulation approaches to evaluate pharmacokinetic sampling contamination from central venous catheters in pediatric pharmacokinetic studies of actinomycin-D: a report from the children's oncology group.
Cancer Chemother Pharmacol. 2012; 70(1):83-94 [PubMed] Free Access to Full Article Related Publications
OBJECTIVES: To develop a population pharmacokinetic model of actinomycin-D (AMD) in children with cancer incorporating expressions for drug contamination from PK samples obtained via indwelling CVLs and to evaluate the efficiency of a catheter clearing procedure in removing contamination as well as the impact of contamination on PK results.
METHODS: A dataset of 199 AMD plasma concentration measurements from 36 patients (age 1.6-20.3 years) was analyzed using nonlinear mixed-effects modeling. Quantitative modeling approaches, including baseline contamination model, covariate model, and catheter clearance model, were evaluated to describe catheter contamination. Monte Carlo simulations mimicking a prospective study in children with cancer were performed to assess the performance of the final model and impact of catheter contamination on PK reporting.
RESULTS: The PK of AMD was best described by a linear 3-compartment model with first-order elimination. A baseline contamination model including a contamination factor proportional to the model-predicted concentration for samples obtained from central catheters was chosen as the most parsimonious and accurate among competing models. The final model parameters were allometrically scaled to a 70 kg person. The estimated mean parameter values were 11 L/h, 5.79, 24.2, 490 L, 17.7, and 42.8 L/h for total clearance, central volume of distribution, peripheral volume 1, peripheral volume 2, inter-compartmental clearance 1, and inter-compartmental clearance 2, respectively. The proportional contamination factor was 19.3 % immediately post-drug administration and decreased at a first-order rate of 0.0932 h(-1). Simulations precisely re-estimated kinetic parameters with catheter contamination adjustment. Large uncertainty and poor estimation were observed when contamination was ignored.
CONCLUSIONS: Drug contamination from sampling catheter can impact AMD PK results and should be accounted for in the analysis. We provide a framework for evaluating catheter contamination and guidance on adjustment in the PK model.
Combination of TRAIL and actinomycin D liposomes enhances antitumor effect in non-small cell lung cancer.
Int J Nanomedicine. 2012; 7:1449-60 [PubMed] Free Access to Full Article Related Publications
Rhabdomyosarcoma of the orbit in a four months old infant in Zimbabwe: A case report.
Cent Afr J Med. 2012 May-Aug; 58(5-6):26-9 [PubMed] Related Publications
Treatment of nonmetastatic and metastatic low-risk gestational trophoblastic neoplasia: factors associated with resistance to single-agent methotrexate chemotherapy.
Gynecol Oncol. 2012; 125(3):572-5 [PubMed] Related Publications
METHODS: We reviewed the records of 358 patients with low-risk GTN (FIGO stage I and stages II-III, score<7) treated initially with methotrexate 0.4 mg/kg (max 25mg) IV push daily × 5 days every 14 days between 1979 and 2009. Actinomycin D 0.5mg IV push daily × 5 days every 14 days was used in 64 patients who developed resistance or toxicity to initial methotrexate chemotherapy, and combination drug regimens were used in 20 patients who failed single-agent chemotherapy. Adjuvant surgery was used in 34 selected patients. Clinical response and survival as well as factors affecting outcomes were analyzed retrospectively.
RESULTS: The complete response rate to initial methotrexate chemotherapy was 81% (290/358) and the complete response rate to actinomycin D as secondary therapy was 75% (48/64), for an overall complete response rate to sequential single-agent chemotherapy of 94% (338/358). The remaining 20 patients (6%) were all placed into permanent remission with the use of multiagent chemotherapy with or without surgery. Resistance to initial methotrexate chemotherapy was associated with increasing FIGO score (p<.0001), clinicopathologic diagnosis of choriocarcinoma (p=.028), higher pretreatment hCG (p=0.001) and presence of metastatic, disease (p=.018).
CONCLUSIONS: Sequential single-agent chemotherapy with methotrexate (0.4 mg/kg-max 25mg) followed by actinomycin D (0.5mg) each given IV push for 5 consecutive days every other week for treatment of low-risk GTN resulted in only 6% of patients requiring multiagent chemotherapy and a 100% survival rate.
A multi-institutional experience of repeat regional chemotherapy for recurrent melanoma of extremities.
Ann Surg Oncol. 2012; 19(5):1637-43 [PubMed] Free Access to Full Article Related Publications
METHODS: Data from 44 patients, who underwent repeat HILPs or ILIs from 3 institutions beginning 1997 to 2010, were retrospectively reviewed. Regional toxicity assessed by Wieberdink grade, systemic toxicity assessed by serum creatine phosphokinase level, length of hospital stay (LOS), response rates at 3 months after the procedure, and time to in-field progression (TTP) were analyzed.
RESULTS: Of 44 patients, 46% were men and 54% women with a median age of 66 (range 29-85) years at diagnosis. The median follow-up was 21.4 (range 4-153) months. Of 70 ILIs and 28 HILPs, the following groups were identified: group A, ILI → ILI (n = 25); group B, ILI → HILP (n = 10); group C, HILP → ILI (n = 12); and group D, HILP → HILP (n = 3). The comparison of Wieberdink grade, serum creatine phosphokinase level, LOS, and response rate between procedures (HILP vs. ILI), between sequence (initial vs. repeat), and among their interactions showed no statistically significant differences. TTP after initial procedure did not differ between HILP and ILI (P = 0.08), and no survival difference was seen (P = 0.65) when TTP after repeat procedure was compared.
CONCLUSIONS: Most patients tolerated repeat regional chemotherapy without increased toxicity or LOS. No statistical difference in clinical outcomes was noted when comparing repeat procedures, even though repeat HILPs showed higher complete response compared to repeat ILIs.
Comparison of pulsed actinomycin D versus 5-day methotrexate for the treatment of low-risk gestational trophoblastic disease.
Int J Gynaecol Obstet. 2012; 116(1):39-42 [PubMed] Related Publications
METHODS: From 2008 until 2010, 75 women with low-risk gestational trophoblastic disease received either pulsed actinomycin D (n=50) or 5-day methotrexate (n=25). The primary remission rate, the duration of treatment, the number of treatment courses, and the adverse effects were compared.
RESULTS: The complete remission rates were 90% for the actinomycin D group and 68% for the methotrexate group (P=0.018). The mean number of chemotherapy courses administered to achieve complete remission (including courses of second-line therapy) was 3.1 in the methotrexate group and 5.3 in the actinomycin D group (P=0.01). No major adverse effects were experienced in either treatment group and there were no significant differences in terms of adverse effects. Second-line chemotherapy was indicated for 11 patients.
CONCLUSION: Based on the present study, pulsed actinomycin D seems to be an appropriate first-line treatment for patients with low-risk gestational trophoblastic disease.
Technique and outcomes of isolated limb infusion for locally advanced malignant melanoma--a radiological perspective.
Clin Radiol. 2011; 66(12):1175-80 [PubMed] Related Publications
MATERIALS AND METHODS: A retrospective analysis of 11 patients who underwent 12 procedures between 2005 and 2009 was performed. Pre-procedural staging computed tomography (CT), CT angiography, and duplex studies were performed. All patients received a cytotoxic combination of melphalan and actinomycin-D via radiologically placed arterial and venous catheters in the affected limb under mild hyperthermic conditions. The outcome measures include response rates, limb toxicity, complications, and survival.
RESULTS: All patients were female with a mean age of 72 years. Three patients had American Joint Committee on Cancer (AJCC) stage IIIB melanoma, seven had stage IIIC melanoma, and one had a stage IIIB Merkel cell tumour. Complete response was seen in five patients (46%), partial response in four (36%), and progressive disease in two (18%). One patient developed grade 4 toxicity requiring a fasciotomy and another experienced systemic toxicity.
CONCLUSION: These outcomes are comparable to previous studies and shows that ILI is effective in locoregional control of unresectable melanoma. It is a relatively safe procedure but not without risk. Our experience shows the importance of radiological input to ensure safe and effective delivery of services.
Evaluation of an Actinomycin D/VX-680 aurora kinase inhibitor combination in p53-based cyclotherapy.
Oncotarget. 2010; 1(7):639-50 [PubMed] Free Access to Full Article Related Publications