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Dose escalation study of an anti-thrombocytopenic agent in patients with chemotherapy induced thrombocytopenia.

Levin RD, Daehler M, Grutsch JF, Hall JL, Gupta D, Lis CG - BMC Cancer (2010)

Bottom Line: Preclinical studies demonstrated that small chain RNA fragments accelerate the recovery of platelets numbers in animals exposed to high doses of chemotherapeutic drugs.Subjects kept a diary indicating RNA fragment and magnesium administration, and any experienced side effects.These data indicate that 60 and 80 mg doses of E. coli RNA accelerated platelet recovery.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cancer Treatment Centers of America® at Midwestern Regional Medical Center, Zion IL, USA. jfgrutsch@yahoo.com.

ABSTRACT

Background: Preclinical studies demonstrated that small chain RNA fragments accelerate the recovery of platelets numbers in animals exposed to high doses of chemotherapeutic drugs. There is anecdotal data supporting the same application in humans. The Phase I clinical trial described here was designed to investigate the relationship between the administration of small chain RNA fragments and the recovery in platelets following Chemotherapy-Induced Thrombocytopenia (CIT).

Methods: Cancer patients with solid tumors that experienced post chemotherapy thrombocytopenia with a nadir of < = 80,000 platelets/ml were eligible for this clinical trial. There were no exclusions based on ECOG status, tumor type, tumor burden or chemotherapeutic agents. Patients received a unique preparation of RNA derived from either E. coli or yeast. Ten patients per group received 20, 40, or 60 mg as a starting dose. Subjects self-administered RNA fragments sublingually on an every other day schedule while undergoing chemotherapy. The dose was escalated in 20 mg increments to a maximum dose of 80 mg if the nadir was < 80,000 platelets/ml at the start of the next cycle. Subjects were treated for three cycles of chemotherapy with the maximum effective dose of RNA fragments. Subjects continued on planned chemotherapy as indicated by tumor burden without RNA fragment support after the third cycle. Subjects kept a diary indicating RNA fragment and magnesium administration, and any experienced side effects.

Results: Patients receiving E. coli RNA fragments demonstrated a more rapid recovery in platelet count and higher nadir platelet count. None of the patients receiving the E. coli RNA fragments required a chemotherapy dose reduction due to thrombocytopenia. The optimal dose for minimizing CIT was 80 mg. Conversely, subjects receiving yeast RNA fragments with dose escalation to 80 mg required a chemotherapy dose reduction per American Society of Clinical Oncology guidelines for grade 3 and 4 thrombocytopenia.

Conclusions: Patients receiving myelosuppressive chemotherapy experienced an improvement in the platelet nadir and shorter recovery time when receiving concurrent E coli RNA fragments, when compared to patients who received yeast RNA fragments. These data indicate that 60 and 80 mg doses of E. coli RNA accelerated platelet recovery. Further clinical investigations are planned to quantify the clinical benefits of the E. coli RNA at the 80 mg dose in patients with chemotherapy induced thrombocytopenia.

Trial registration: Clinical Trials.gov Identifier: NCT01163110.

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Breast Cancer Patient with Metastatic Disease to Flat Bones with Two Prior Chemotherapy Regimens--Current Regimen is Doxorubicin.
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Figure 1: Breast Cancer Patient with Metastatic Disease to Flat Bones with Two Prior Chemotherapy Regimens--Current Regimen is Doxorubicin.

Mentions: This clinically heterogeneous group of patients likely had a wide distribution in bone marrow reserve. Consequently, we examined whether there were any differences in the distribution of platelet counts at the time of first administration of RNA fragments or at dose escalation of the RNA fragments at day 1 of chemotherapy. There was no statistically significant difference in the platelet count by E. coli RNA fragment dose. The platelet levels one day 1 of chemotherapy were 162000/ml (treatment cycle number = 12), 177,500/ml (treatment cycle N = 25), 160000/ml (treatment cycle N = 21), and 187,000/ml (treatment cycle N = 47) for 20 mg, 40 mg, 60 mg and 80 mg respectively (Kruskal-Wallis P = 0.086). All of the patients on E. coli RNA fragments showed an oscillation in platelet counts where the platelet levels declined after the administration of chemotherapy and recovered during the rest phase of the treatment cycle, Figure 1. There was no statistically significant difference in the median time to chemotherapy induced platelet nadirs by RNA fragment dose (Kruskal-Wallis P = 0. 841). There was no statistically significant difference in the platelet counts in chemotherapy induced nadirs by fragment dose, or in the prevalence of nadir levels less than 25000/ml, which was 16.6%, 21%, 10%, and 24% for 20, 40, 60, and 80 mg levels respectively. The prevalence rate for nadir levels greater than 80000/ml, was 8.3%, 33%, 20%, and 28%, respectively for 20, 40, 60, and 80 mg indicating the relative failure of the 20 mg dose. This trend was a statistically significant (p < .05). Finally, there was a statistically significant shortening in time from chemotherapy induced nadir to attaining recovery platelet level of 80000/ml or more from a median recovery time of eight days for the 20 mg dose to a median time to recovery of 6 or 7 days for the other doses (Kruskal-Wallis P = 0.044).


Dose escalation study of an anti-thrombocytopenic agent in patients with chemotherapy induced thrombocytopenia.

Levin RD, Daehler M, Grutsch JF, Hall JL, Gupta D, Lis CG - BMC Cancer (2010)

Breast Cancer Patient with Metastatic Disease to Flat Bones with Two Prior Chemotherapy Regimens--Current Regimen is Doxorubicin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2967549&req=5

Figure 1: Breast Cancer Patient with Metastatic Disease to Flat Bones with Two Prior Chemotherapy Regimens--Current Regimen is Doxorubicin.
Mentions: This clinically heterogeneous group of patients likely had a wide distribution in bone marrow reserve. Consequently, we examined whether there were any differences in the distribution of platelet counts at the time of first administration of RNA fragments or at dose escalation of the RNA fragments at day 1 of chemotherapy. There was no statistically significant difference in the platelet count by E. coli RNA fragment dose. The platelet levels one day 1 of chemotherapy were 162000/ml (treatment cycle number = 12), 177,500/ml (treatment cycle N = 25), 160000/ml (treatment cycle N = 21), and 187,000/ml (treatment cycle N = 47) for 20 mg, 40 mg, 60 mg and 80 mg respectively (Kruskal-Wallis P = 0.086). All of the patients on E. coli RNA fragments showed an oscillation in platelet counts where the platelet levels declined after the administration of chemotherapy and recovered during the rest phase of the treatment cycle, Figure 1. There was no statistically significant difference in the median time to chemotherapy induced platelet nadirs by RNA fragment dose (Kruskal-Wallis P = 0. 841). There was no statistically significant difference in the platelet counts in chemotherapy induced nadirs by fragment dose, or in the prevalence of nadir levels less than 25000/ml, which was 16.6%, 21%, 10%, and 24% for 20, 40, 60, and 80 mg levels respectively. The prevalence rate for nadir levels greater than 80000/ml, was 8.3%, 33%, 20%, and 28%, respectively for 20, 40, 60, and 80 mg indicating the relative failure of the 20 mg dose. This trend was a statistically significant (p < .05). Finally, there was a statistically significant shortening in time from chemotherapy induced nadir to attaining recovery platelet level of 80000/ml or more from a median recovery time of eight days for the 20 mg dose to a median time to recovery of 6 or 7 days for the other doses (Kruskal-Wallis P = 0.044).

Bottom Line: Preclinical studies demonstrated that small chain RNA fragments accelerate the recovery of platelets numbers in animals exposed to high doses of chemotherapeutic drugs.Subjects kept a diary indicating RNA fragment and magnesium administration, and any experienced side effects.These data indicate that 60 and 80 mg doses of E. coli RNA accelerated platelet recovery.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cancer Treatment Centers of America® at Midwestern Regional Medical Center, Zion IL, USA. jfgrutsch@yahoo.com.

ABSTRACT

Background: Preclinical studies demonstrated that small chain RNA fragments accelerate the recovery of platelets numbers in animals exposed to high doses of chemotherapeutic drugs. There is anecdotal data supporting the same application in humans. The Phase I clinical trial described here was designed to investigate the relationship between the administration of small chain RNA fragments and the recovery in platelets following Chemotherapy-Induced Thrombocytopenia (CIT).

Methods: Cancer patients with solid tumors that experienced post chemotherapy thrombocytopenia with a nadir of < = 80,000 platelets/ml were eligible for this clinical trial. There were no exclusions based on ECOG status, tumor type, tumor burden or chemotherapeutic agents. Patients received a unique preparation of RNA derived from either E. coli or yeast. Ten patients per group received 20, 40, or 60 mg as a starting dose. Subjects self-administered RNA fragments sublingually on an every other day schedule while undergoing chemotherapy. The dose was escalated in 20 mg increments to a maximum dose of 80 mg if the nadir was < 80,000 platelets/ml at the start of the next cycle. Subjects were treated for three cycles of chemotherapy with the maximum effective dose of RNA fragments. Subjects continued on planned chemotherapy as indicated by tumor burden without RNA fragment support after the third cycle. Subjects kept a diary indicating RNA fragment and magnesium administration, and any experienced side effects.

Results: Patients receiving E. coli RNA fragments demonstrated a more rapid recovery in platelet count and higher nadir platelet count. None of the patients receiving the E. coli RNA fragments required a chemotherapy dose reduction due to thrombocytopenia. The optimal dose for minimizing CIT was 80 mg. Conversely, subjects receiving yeast RNA fragments with dose escalation to 80 mg required a chemotherapy dose reduction per American Society of Clinical Oncology guidelines for grade 3 and 4 thrombocytopenia.

Conclusions: Patients receiving myelosuppressive chemotherapy experienced an improvement in the platelet nadir and shorter recovery time when receiving concurrent E coli RNA fragments, when compared to patients who received yeast RNA fragments. These data indicate that 60 and 80 mg doses of E. coli RNA accelerated platelet recovery. Further clinical investigations are planned to quantify the clinical benefits of the E. coli RNA at the 80 mg dose in patients with chemotherapy induced thrombocytopenia.

Trial registration: Clinical Trials.gov Identifier: NCT01163110.

Show MeSH
Related in: MedlinePlus