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At least 19 recordsLinked to original sources
PubMed1992

Determination of plicamycin in plasma by radioimmunoassay.

This article describes a method for the determination of plicamycin in plasma by radioimmunoassay. The anti-plicamycin antibody was produced against a plicamycin-bovine serum albumin conjugate prepared by using diazotized p-aminobenzoic acid as a cross-linker. The radiolabeled ligand, 125I-plicamycin, was prepared by the chloramine-T method. The linear plicamycin concentration range was 7-400 ng/ml. The coefficients of variation for intra- and interday variabilities were 7.5 and 15%, respectively. No interference was observed from either the structurally related chromomycin A or concomitantly used drugs hydroxyurea or allopurinol. With this method of testing, plicamycin levels in plasma could be determined in patients receiving small (0.85-1.0 mg/m2) therapeutic plicamycin doses. Preliminary pharmacokinetic data in humans indicate that the plasma drug disappearance curve was biphasic with a mean elimination half-life of 10.6 +/- 1.7 h, total clearance rate of 11.1 +/- 0.4 ml/min/m2, and area under the plasma drug concentration-time curve of 1,289-1,546 ng-h/ml. This assay method is clinically useful for pharmacokinetic studies of plicamycin and may be helpful in the design of rational therapeutic drug trials.

Antibody Specificity↗
PubMed1992

Possible severe thrombocytopenia associated with a single dose of plicamycin.

OBJECTIVE: To report a case of possible severe thrombocytopenia associated with administration of a single dose of plicamycin. CASE SUMMARY: A 73-year-old man with prostate cancer was admitted to the hospital with hypercalcemia (total serum calcium concentration 4.02 mmol/L) and a low baseline platelet count (152 x 10(9)/L). Because of his symptomatic hypercalcemia, he was treated with NaCl 0.9%, furosemide, oral inorganic phosphate, and a single dose of plicamycin (15 micrograms/kg). Five days after plicamycin administration his platelet count decreased to 52 x 10(9)/L, and continued to decrease further even after the transfusion of four units of platelets to a nadir of 7 x 10(9)/L (hospital day 20). A second transfusion produced a small increase in his platelet count. The patient's clinical status continued to deteriorate, however, and he subsequently died. DISCUSSION: Plicamycin and other drugs that may induce thrombocytopenia are reviewed. The time course between plicamycin administration and the development of thrombocytopenia in our patient is assessed. Other contributing factors such as a low baseline platelet count and advanced age are also addressed. CONCLUSIONS: It is likely that the severe thrombocytopenia experienced by our patient was caused by a single dose of plicamycin. Adjusting the dosage for a patient's renal function as well as close monitoring of the platelet count are necessary when administering this drug. We report this case to remind clinicians of the potential for the development of severe thrombocytopenia following administration of a single dose of plicamycin.

Aged↗
PubMed1992

Plicamycin and pamidronate in symptomatic tumor-related hypercalcemia: a prospective randomized crossover trial.

We have conducted a randomized crossover comparative trial of a single-dose course of disodium (3-amino-1-hydroxypropylidene) bisphosphonate pentahydrate (pamidronate) and plicamycin in 48 patients with a first occurrence of tumor-related hypercalcemia. All patients had hypercalcaemia-associated symptoms and serum-calcium levels (corrected for total protein) greater than or equal to 2.80 mmol/l. Pamidronate and plicamycin were given concurrently with rehydration immediately after diagnosis of hypercalcaemia was made. Both agents lowered serum calcium levels significantly within 1 week, with 88% of the evaluable patients in the pamidronate group and 45% of those in the plicamycin group achieving normocalcemia (p less than 0.01). In the patients who received pamidronate, the duration of normocalcemia was longer (p less than 0.05) and there was a significant decrease in serum creatinine (p less than 0.05). Vomiting occurred in 8 of 22 evaluable patients (36%) who received plicamycin, but in none of 25 evaluable patients who received pamidronate (P less than 0.01). Phlebitis occurred at the infusion site in more of the pamidronate-treated patients (P less than 0.05). Hypocalcemia, which occurred in 8 of 25 evaluable patients (32%) in the pamidronate group and in 1 of 22 of those (5%) in the plicamycin group, was either clinically asymptomatic or mild, except in one pamidronate-treated patient. Overall, pamidronate was found to be more effective and better tolerated than plicamycin, thereby confirming results of previous studies that showed pamidronate to be an effective, simple, and safe agent for the relief of the morbidity associated with tumor-related hypercalcemia.

Adult↗
PubMed1987

Differentiation of blasts from patients in myeloid crisis of chronic myelogenous leukemia by in-vivo and in-vitro plicamycin treatment.

Two cases in myeloid blast phase of chronic myelogenous leukemia (CML) responded to treatment with plicamycin alone. Their total white blood cell (WBC) count and immature myeloid cells fell in one case rapidly and in the other gradually. Approximately two to three weeks after initiation of plicamycin their total WBC count began to rise again, whereas the mature myeloid cells remained constant throughout the treatment. These results suggest that plicamycin may be effective in suppressing proliferation of blasts and promoting their maturation in the myeloid blast phase of CML, but that plicamycin alone may not be effective enough to sustain duration of response.

Adult↗
PubMedDate not supplied

[P-glycoprotein and treatment with plicamycin + hydroxyurea in myeloid blastic crisis of chronic myeloid leukemia].

The authors studied P-glycoprotein (P-gp) expression in three patients affected by myeloid blast crisis of chronic myeloid leukemia undergoing chemotherapy with plicamycin + hydroxyurea. P-gp is the molecular marker of multidrug resistance (MDR), and is able to promote the efflux of various drugs (including plicamycin) from the neoplastic cell. When resistance towards plicamycin and hydroxyurea association was observed, the blasts obtained from the three patients were found to express P-gp. Although P-gp may be not the unique mechanism responsible for resistance towards plicamycin and hydroxyurea association, the MDR phenotype may play an important role in the resistance towards this treatment protocol in the blast crisis of chronic myeloid leukemia.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1986

Preliminary observations on the therapy of the myeloid blast phase of chronic granulocytic leukemia with plicamycin and hydroxyurea.

We observed a dramatic improvement in the peripheral blood counts of a patient in the myeloid blast phase of chronic granulocytic leukemia after plicamycin (mithramycin) therapy of concurrent hypercalcemia. We then treated eight additional patients in the blast phase of chronic granulocytic leukemia with a combination of alternate-day plicamycin and daily hydroxyurea. All six patients with myeloid morphology at the time of blast crisis responded with a return to a chronic phase without an intervening pancytopenic period. Of three patients with lymphoid morphology at the time of treatment, only one responded (this patient had recently relapsed and converted from myeloid to lymphoid morphology). Another patient with nonmyeloid, nonlymphoid blast morphology also did not respond. Continual therapy with the two-drug combination appeared to be necessary, since early relapses were seen in responding patients whose therapy was interrupted. These data are preliminary and will need further confirmation, but they suggest that the combination of alternate-day plicamycin and daily hydroxyurea may be effective in the myeloid blast phase of chronic granulocytic leukemia.

Adult↗
PubMed1997

A pilot study of alpha-interferon and plicamycin for accelerated phase of chronic myeloid leukemia.

Thirteen patients with accelerated phase of chronic myeloid leukemia (CML-AC) were treated with intravenous plicamycin and subcutaneous alpha-interferon. Two patients stabilized, three patients had partial hematologic responses and one patient had a hematologic complete response with a major cytogenetic response. Two patients, progressing on hydroxyurea, did not respond, but demonstrated re-sensitization to hydroxyurea after completion of induction therapy and had prolonged return to chronic phase for 30 months and 25 months. Four non-responders subsequently received additional chemotherapy and responded. Median survival of all study patients from the development of accelerated phase of CML was 24 months: substantially longer than other reported series (median 6 months). Plicamycin appears to add efficacy to interferon in the stabilization of accelerated phase of CML.

Adult↗
PubMed1989

Metastatic carcinoma of unknown primary: complete response to second-line treatment with plicamycin.

In selected groups of patients, metastatic carcinoma of unknown primary (MCUP) is highly responsive to cisplatin-based combination chemotherapy. These therapeutic responses usually are partial and shortlived. The authors report the case of a 41-year-old man whose MCUP relapsed after responding to cisplatin, bleomycin, and etoposide. Alternate-day treatment with plicamycin induced a second complete remission (CR) in this patient with minimal hematologic and metabolic toxicity. Plicamycin may prove effective in enhancing CR rate, prolonging CR duration, and salvaging cisplatin failures in MCUP.

Adult↗
PubMed1995

Long-term follow-up of stage III testicular carcinoma treated with mithramycin (plicamycin).

In 1965 we reported mithramycin (plicamycin) to produce objective regression in 7 of 12 patients with advanced testicular carcinoma. Between 1963 and 1975 mithramycin was administered to 62 patients with advanced testicular carcinoma as the initial chemotherapy and to 30 patients who failed to respond to prior chemotherapies. There were 13 complete regressions (23%) in 56 patients who as initial chemotherapy received more than one course of mithramycin. The median follow-up is 23 years with 10 patients still alive. A partial regression occurred in 11 (18%), all of whom are dead. Of 30 patients receiving mithramycin after prior chemotherapies, none had a complete regression, 5 had a partial regression, and all are dead. Of 13 patients undergoing complete regression, 85% never had a recurrence of testicular carcinoma. The median follow-up of 23 years implies that these patients are cured.

Follow-Up Studies↗
PubMed1989

Therapy of the myeloid blast phase of chronic granulocytic leukemia with plicamycin and hydroxyurea.

Treatment of the myeloid blast phase of chronic granulocytic leukemia is still a major problem in clinical hematology. Alternate-day plicamycin and hydroxyurea treatment was reported to induce remissions in the majority of patients with myeloid blast phase by Koller and Miller in 1986 Subsequently we treated eight patients according to this regimen. Complete remissions could not be achieved and no prolongation of median survival was observed. In two patients treatment had to be discontinued due to severe toxicity.

Adult↗
PubMed1989

Phase II trial of plicamycin and hydroxyurea in acute myelogenous leukemia.

A total of 23 patients with high-risk acute myelogenous leukemia (AML) at diagnosis (2 patients), relapsing AML (14) or resistant AML (6) were treated with 25 micrograms/kg i.v. plicamycin every other day for 3 weeks and 500-4,000 mg hydroxyurea per day p. o. according to the WBC count. Aplasia was observed in only two patients. Severe extrahematologic toxicity included sepsis (four cases), vomiting (four patients), toxic hepatitis (three cases), and fibrinopenia (one patient). No partial or complete responses were observed. The 95% confidence interval limit of the overall response rate (CR + PR) was 0-14%.

Bone Marrow↗
PubMedDate not supplied

The plicamycin and hydroxyurea combination chemotherapy for chronic granulocytic leukemia in myeloid transformation.

Between 1987-1988 we treated, in a cooperative study, 13 patients in blast crisis of CGL according to Koller and Miller's regimen. We observed no return to the chronic phase of the disease, while some patients suffered major drug-induced side effects. Six patients in accelerated phase were treated with the same combination therapy. All of them responded with a return to the chronic phase for a median of 4.5 months. In our hands the combination of plicamycin and hydroxyurea was ineffective in patients with CGL in blast crisis. This regimen could deserve further evaluation in patients with CGL in acceleration.

Adult↗
PubMed1987

Actin synthesis in cultured cardiac myocytes: comparative effects of doxorubicin, dactinomycin, and plicamycin.

Cultured neonatal rat myocardial cells (CMC) were incubated with 10(-8) to 10(-5) mol/L doxorubicin (ADR), dactinomycin (ACT), and plicamycin (MIT), respectively, in medium containing 35 mu Ci sulfur 35-labeled methionine to determine comparative effects on myocardial contractile protein synthesis. Cells were harvested in 2 mmol/L Tris buffer with 0.1% Triton X-100, homogenized, and fractionated by centrifugation. Aliquots of the extracts containing equivalent amounts of protein were applied to 8% to 15% gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Similar aliquots were subjected to isoelectric focusing and to gel electrophoresis in the second dimension. All electrophoretic gels were autoradiographed. A concentration-dependent effect of ADR, ACT, and MIT on protein and on actin synthesis was found in cultured myocytes with decreased density of radiolabeled actin band in CMC exposed to either 10(-5) mol/L ADR, or from 10(-8) to 10(-5) mol/L ACT, or from 10(-7) to 10(-5) mol/L MIT. Autoradiographs of two-dimensional gels focused actin isoforms but showed substantial decreases of all actin isoforms in CMC extracts from 10(-7) mol/L ACT. ACT and MIT each decreased CMC protein synthesis by 20% at 10(-8) mol/L. At 10(-6) mol/L ADR, synthesis of alpha-actin was diminished preferentially compared with beta and gamma. Synthesis of all actin isoforms was diminished at 10(-5) mol/L ADR. The effect of MIT and ACT on CMC actin and protein synthesis in heart cells is not as specific as the effect of ADR on CMC actin and protein synthesis.

Actins↗