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PubMed2005

Comparison of pulse methotrexate and pulse dactinomycin in the treatment of low-risk gestational trophoblastic neoplasia.

Methotrexate and dactinomycin are efficient drugs in the treatment of patients with low-risk gestational trophoblastic neoplasia (LRGTN). To compare the effectiveness of these two drugs in LRGTN, 46 patients were randomised to receive weekly intramuscular methotrexate at 30 mg/m(2) (n = 28) or intravenous dactinomycin at 1.25 mg/m(2) every 2 weeks (n = 18). Fourteen patients (50%) in the methotrexate group and 16 patients (89%) in the dactinomycin group achieved complete response. Greater patient convenience and a lower number of required visits make dactinomycin superior to other alternatives.

Adolescent↗

PubMed1978

[Action of aureolic acid and dactinomycin group antibiotics on human brain tumors in culture].

The cytotoxic effect of antitumour antibiotics, such as dactinomycin, mithramycin, variamycin and olivomycin on the cells of the human brain tumours (multiform glyoblastoma, arachnoidendotelioma and astrocytoma) grown by the method of the primary plasmic culture was studied. Dactinomycin was superior to the antibiotics of the aureolic acid group in the rate and level of the cytotoxic effect on the tumour cells: 76 per cent of the above tumours were sensitive to dactinomycin, 56 per cent to mithramycin and 52 per cent to variamycin and olivomycin. Among the total number of the tumours sensitive to the drugs the number of the highly sensitive tumours amounted to 57.9 per cent for dactinomycin and 30.8--38.5 per cent for the antibiotics of the aureolic acid group. Definite differences in the efficiency of the antibiotics of the aureolic acid group with respect to different types of the brain tumours were observed.

Antibiotics, Antineoplastic↗

PubMed1979

Late treatment of murine lupus erythematosus with dactinomycin (actinomycin D). I. Course and longevity.

Dactinomycin treatment a of group of (NZB X NZW)F1 hybrid female mice was delayed until the age of 6-6 1/2 months, by which time the immune complex disease was well established. Three animals of the original twenty-eight had already died, ten had heavy proteinuria and a few were oedematous. The dactinomycin dose was 3.5 microgram per day, which was suspended when significant weight loss occurred. Twelve of the thirteen experimental mice were alive at 12 months of age, eleven at 15 months, but only eight by 20 months, whereas all twelve control animals had died by the age of 11 months. These results and the supporting data on body weight and renal function indicate that dactinomycin can at least arrest the disease process and may improve it. The mechanism is not known, but it may be the result of a reduced availability of DNA or an alteration in its properties following combination with dactinomycin.

Animals↗

PubMed1983

Results of retroperitoneal lymph node dissection and postoperative adjuvant chemotherapy with dactinomycin in the treatment of retroperitoneal metastases of nonseminomatous testicular germ cell tumors.

This article discusses 103 patients with a nonseminomatous testicular germ cell tumor. Treatment of 87 patients in clinical Stages I, II-A, and II-B consisted of bilateral retroperitoneal lymph node dissection. In Stage I (54 patients), no further treatment was given. The three-year survival was 96%, while recurrence-free survival was 98%. Of 33 patients in Stages II-A and II-B, 26 received adjuvant chemotherapy with dactinomycin, and ten of these were given radiotherapy (peritoneum/mediastinum) as well. The three-year survival was 88% and recurrence-free survival was 85%. Seven patients in Stages II-A and II-B received no adjuvant chemotherapy; four of them died. Treatment of 14 patients in Stage II-C primarily consisted of dactinomycin therapy, subsequently combined with surgery and radiotherapy. The three-year survival was 28.5%. These findings raise the question whether adjuvant single-agent chemotherapy with dactinomycin for patients with a nonseminomatous testicular germ cell tumor should not be re-evaluated.

Adolescent↗

PubMed2006

Phase II trial of pulse dactinomycin as salvage therapy for failed low-risk gestational trophoblastic neoplasia: a Gynecologic Oncology Group study.

BACKGROUND: The purpose of the study was to determine the activity and toxicity of pulse dactinomycin as salvage treatment of patients with low-risk gestational trophoblastic neoplasia (GTN) who failed methotrexate therapy. METHODS: Eligible patients had persistent/recurrent low-risk GTN defined by changes in serum human chorionic gonadotropin (hCG) levels (<10% fall over 3 consecutive weekly titers, >20% rise over the previous value, or a rise after attaining institutional normal [>5 mu/mL]); World Health Organization (WHO) score 2-6; Gynecologic Oncology Group (GOG) performance status 0-1; and previous treatment restricted to methotrexate. Dactinomycin administration was 1.25 mg/m2 intravenous (i.v.) every 2 weeks until documented complete response (CR) or treatment failure. CR was defined as an institutional normal serum hCG level sustained for >or=4 consecutive weeks; treatment failure was a <10% fall (3 assays over 4 weeks) or >20% rise (over previous value) in hCG serum level. Levels were monitored biweekly x 8 weeks beyond the first normal value, then monthly x 10. RESULTS: Five of 44 enrolled patients were ineligible due to choriocarcinoma and normal pretreatment serum hCG level (2 each), no history of methotrexate (1), and 1 patient with documented phantom hCG syndrome was unevaluable. In all, 28 of 38 (74%) evaluable patients attained CR. The median number of cycles was 4 (range, 2-10). Severe toxicity was minimal, causing no patient to discontinue therapy. All treatment failures achieved a CR after receiving subsequent chemotherapy; 3 patients also underwent hysterectomy. CONCLUSION: Pulse dactinomycin is an active regimen for patients with low-risk GTN who fail previous methotrexate therapy.

Adult↗

PubMed1995

Unusual cutaneous toxicity following treatment with dactinomycin: a report of two cases.

Dactinomycin-induced cutaneous toxicity is rare in pediatric patients not receiving radiation therapy. We describe dactinomycin-related lesions in the axilla, groin, and central line exit site of two children treated for rhabdomyosarcoma, neither of whom had received radiation treatment. One patient was initially treated with systemic antifungal therapy, and developed recurrent lesions on reexposure to the drug. The other was noted to have mild, diffuse hyperpigmentation. Skin biopsies revealed interface dermatitis with syringometaplasia in both cases. Both children recovered uneventfully within 4 weeks. Recognition of unusual rashes with a characteristic distribution in patients receiving dactinomycin should aid in diagnosis, and help avoid unnecessary therapeutic procedures.

Child↗

PubMedDate not supplied

Dactinomycin-induced, severe lichenoid eruption in a child.

There is little information in the medical literature about skin rashes associated with dactinomycin in the absence of radiotherapy. We report a 12-month-old male child who developed a severe cutaneous reaction that consisted of a widespread pruritic papular eruption associated with fever and a poor general state after dactinomycin administration. Skin biopsy specimen findings confirmed the diagnosis of lichenoid eruption. The rash improved with topical steroid treatment and completely resolved within 1 month with persistence of a residual mild hyperpigmentation. Dactinomycin administration was discontinued for the remaining cycles of chemotherapy.

Antibiotics, Antineoplastic↗

PubMed1991

Hepatopathy-thrombocytopenia syndrome--a complication of dactinomycin therapy for Wilms' tumor: a report from the United Kingdom Childrens Cancer Study Group.

We have observed hepatopathy, associated with thrombocytopenia, in children receiving chemotherapy for Wilms' tumor. We have studied this hepatopathy-thrombocytopenia syndrome (HTS) in patients enrolled in the United Kingdom Childrens' Cancer Study Group (UKCCSG) Wilms' tumor trials (UKW1 and UKW2). At the time of this study, 501 patients had completed therapy. Treatment flow sheets were examined for evidence of hepatopathy (hepatomegaly with abnormal liver function tests) and severe thrombocytopenia (platelet count less than 25 x 10(9)/L). No child who developed the syndrome had received irradiation. HTS was seen in five of 355 (1.4%) of patients treated with combination chemotherapy but in none of the 146 patients treated with vincristine alone. In each instance, the onset was less than 10 weeks after diagnosis. In two children, hepatopathy was severe with jaundice, ascites, transaminases greater than 1,000 IU/L, and prolongation of prothrombin time. On average, HTS lasted 12 days, and resolved with supportive treatment. After recovery, the children tolerated chemotherapy, mostly at reduced dosage, without recurrence. There was no evident long-term morbidity. Dactinomycin is the probable cause of this syndrome. We conclude that the HTS is a rare but important complication of dactinomycin-containing combination chemotherapy for Wilms' tumor. Children developing "isolated" thrombocytopenia following dactinomycin are "at risk" of developing the full-blown syndrome and should have their treatment modified accordingly.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1976

Effects of dactinomycine (actinomycine D) on budless hydra and during its budding process.

The effect of dactinomycine (actinomycine D) is manifested in various ways, which depends upon its concentration and animal condition at the time of treatment. Dactinomycine is citotoxic in stronger concentations so hydra dies quickly. In thinner concentrations it stops the mitotic activity of the cell, but the basic metabolic processes continue as before. Interstitial cells differenciate into cnidoblasts for some time, the cnid production is not halted, but all of these cells disappear as well as zimogen cells which dedifferentiate into gastrodermal interstitial and into mucous cells. Such animals live longer but die eventually. The effect of dactinomycine is generally milder on animals with a larger cell mass, in hydras with the budding tendency where exist such reserves and in those hydras in which the budding process has begun. In these a part of mobile undamaged zimogen cells can remain. They keep their reproduction ability. These animals can survive and keep on growing normally.

Animals↗

PubMed1983

Treatment of metastatic carcinoid tumor with dactinomycin or dacarbazine.

We studied the effect of two single drugs on patients with metastatic carcinoid tumors. All patients had symptomatic and measurable disease and all had elevations of urinary 5-hydroxy indole acetic acid excretion. Seventeen patients were treated with dactinomycin at a dose of 12-15 micrograms/kg/day for 5 days repeated every 4-5 weeks. One partial response was achieved. Fifteen patients were treated with dacarbazine (DTIC) at a dose of 250 mg/m2/day for 5 days every 4-5 weeks. Two partial responses were achieved. The median times to tumor progression were 10 weeks with dactinomycin and 18 weeks with DTIC. Median survival times were 28 and 47 weeks, respectively. Dactinomycin given by this schedule appears to have only limited activity as a single-agent treatment in malignant carcinoid tumor. DTIC, although showing only a slightly better response rate, perhaps warrants further investigation in view of our more favorable interval to tumor progression and survival experience and in view of this drug's more established activity in the closely related islet cell carcinoma.

Adult↗

PubMed1977

Combination chemotherapy with bleomycin, cyclophosphamide and dactinomycin for the treatment of osteogenic sarcoma.

Thirteen patients with osteogenic sarcoma were treated with multiple drug chemotherapy consisting of bleomycin, cyclophosphamide and dactinomycin. The dosage schedule used was: bleomycin 12 mg/m2/day, cyclophosphamide 600 mg/m2/day, and dactinomycin 450 microgram/m2/day. All drugs were given intravenously for two consecutive days. Treatment was repeated every 2 weeks. Toxicity included severe nausea and vomiting (managed with antiemetics and intravenous hydration) and manifestations of bone marrow depression. Of 13 patients, eight were previously treated with high dose methotrexate with citrovorum factor rescue, cyclophosphamide and Adriamycin. Of these eight, three patients had objective evidence of tumor regression (37.5%). Five of five previously untreated patients had objective evidence of tumor regression. The overall response rate in osteogenic sarcoma patients to BCD was 61.5%. The combination of BCD appears to be more active against osteogenic sarcoma than cyclophosphamide alone or Adriamycin alone. The relative safety with which BCD can be administered makes this combination a valuable adjunct to high dose methotrexate with citrovorum factor rescue and Adriamycin in the treatment of osteogenic sarcoma.

Adolescent↗

PubMed1989

Alternating methotrexate and dactinomycin in nonmetastatic gestational trophoblastic disease.

Alternating 5-day chemotherapy with methotrexate and dactinomycin as primary therapy for nonmetastatic gestational trophoblastic disease was studied in nine patients. The complete response rate was 100% with follow-up of a median of 80 months. Stomatitis was universal but rarely prevented oral alimentation or delayed therapy. Overall, 94% of toxicity was mild or moderate in severity and all toxicity was reversible. This alternating non-cross resistant regimen, reported in a total of 40 patients in the literature, is the only regimen to result in a 100% response rate. This response rate is statistically improved when compared to historical controls receiving methotrexate/folinic acid or pulse dactinomycin. No patients required hysterectomy for disease control. Cooperative prospective phase III studies are needed to determine the efficacy and toxicity of current regimens.

Adult↗

PubMed2004

Dactinomycin-induced veno-occlusive disease in rats. The hepatoprotective action of amifostine. Evaluation in a light and electron microscope.

The purpose of the study was to draw upan experimental model of hepatic veno-occlusive disease (VOD) induced by dactinomycin (ACT) and to investigate the possible hepatoprotective effects of Ethyol (amifostine). Pathological changes corresponding to a VOD picture of varying intensification were found in the liver samples obtained from all the rats receiving ACT. Amifostine appears to act protectively to liver changes caused by dactinomycin.

Amifostine↗

PubMed1978

Dactinomycin treatment of murine lupus erythematosus. I. Renal disease and longevity.

Three groups of female (NZB X NZW)F1 hybrid mice were treated with an intermittent regimen of dactinomycin (actinomycin D), 3.5 microgram. daily. Median survival was doubled in two of the groups and increased by more than 75 per cent in the third. Most of the treated animals never had significant proteinuria. When kidneys from 14 treated mice, which died between the ages of 11 and 20 months, were examined by light and fluorescence microscopy, most showed the lesions of normal aged CBA and C57BL/6 mice, some expansion of the mesangial matrix and increased cellularity, consistent with deposition of immunoglobulins and complement components in the mesangium, generally sparing the capillary loops. Four of the 14 animals, three of them long-lived, had advanced renal glomerular disease. These data indicate that dactinomycin, by whatever therapeutic mechanism, permits very extended survival of B/W female mice, the large majority of them without significant renal disease.

Animals↗

PubMed1985

Single-dose dacarbazine and dactinomycin in advanced malignant melanoma.

Twenty-one patients with advanced malignant melanoma were treated with dacarbazine at a dose of 800 mg/m2 as a single infusion and dactinomycin at a dose of 1.2 mg/m2 every 3 weeks. Hematologic toxicity was mild and gastrointestinal toxicity was tolerable. The response rate for evaluable patients was 22%, which included both men and women with visceral disease. Three of the four responses were complete. Durations of response were 4, 6, 9, and 48+ months. We conclude that dacarbazine can be safely and effectively given as a single dose along with dactinomycin. The possibility that this combination may be more effective than single agents in obtaining complete responses in patients with visceral disease must be explored further.

Adult↗

PubMed1978

[Experimental study of the organotropic properties of dactinomycin].

Dactinomycin was studied pharmacologically on experimental animals. When dactinomycin was administered to the test-animals in doses close to the therapeutic ones for humans, suppression of the bone marrow blood formation was registered in spite of some increase in the number of the reticulocytes and thrombocytes in the peripheral blood and acceleration of the process of blood coagulation. In addition, the urea nitrogen blood levels increased. When the drug was administered in higher doses, suppression of the bone marrow blood formation was pronounced and the number of the leucocytes, reticulocytes and thrombocytes in the peripheral blood decreased. The rate of the blood coagulation decreased, while the biochemical values of the blood were indicative of impairement of the liver and kidney functions.

Animals↗

PubMed1981

Effects of ultraviolet light (2535 A) and dactinomycin upon hydra (Pelmatohydra oligactis).

Hydras exposed to ultraviolet light (2535 A, 12 erg/mm-2/s-2) for 15 minutes suffer a depression immediately, individuals that survived recover quickly and lastingly. Hydras treated with dactinomycin of specific concentrations do not suffer a depression until several days later, do not recover and die eventually. The results are also comparable when hydras are exposed to light and treated with cytostatic of such concentration. In even milder solution of dactinomycin all unexpected hydras recover and survive. But, almost all of the hydras exposed to ultraviolet light and treated with this solution die eventually. The effect of ultraviolet light upon them is then distinctly adverse. Buds are much less damaged and they do not die in this concentration. They grow and reproduce normally. This paper deals with the above mentioned phenomena.

Animals↗

PubMed1994

Alternating weekly chemotherapy with etoposide-methotrexate-dactinomycin/cyclophosphamide-vincristine for high-risk gestational trophoblastic disease.

OBJECTIVE: To evaluate the response rate and toxicity of alternating weekly therapy with etoposide-methotrexate-dactinomycin/cyclophosphamide-vincristine for women with high-risk gestational trophoblastic disease. METHODS: Twenty-two women with gestational trophoblastic disease received 126 cycles of the study regimen. Response was evaluated by serial hCG monitoring. Toxicity was assessed using standard criteria. RESULTS: Six women (27%) were treated for primary therapy and 16 (73%) for secondary therapy. The median prognostic index score was 11 (range 7-19). Only 23% of the patients and 11% of the 126 treatment cycles had grade 4 neutropenia, despite the heavily pretreated patient population. Only 2% of the cycles were associated with neutropenic sepsis or required platelet transfusions. Nonhematologic toxicity was modest. Among 16 women who received chemotherapy alone, there were 11 (69%) complete and three (19%) partial responses. When adjuvant therapies are included, the overall complete and partial response rates were 77 and 14%, respectively. Six (35%) of 17 complete responders developed recurrences. Five patients with partial response or relapse were salvaged with additional therapy. Fifteen of the 22 patients (68%) have sustained remissions. CONCLUSION: The regimen of alternating weekly etoposide-methotrexate-dactinomycin/cyclophosphamide-vincristine is effective and well-tolerated chemotherapy for patients with high-risk gestational trophoblastic disease.

Antineoplastic Combined Chemotherapy Protocols↗