Pentostatin

Pentostatin is a nucleoside analog and also is a potent inhibitor of adenosine deaminase. It has a broad spectrum of immunomodulatory activities. [1] The capacity of this purine analogue to inhibit proliferation and to induce apoptosis of T-cells in combination with its mild toxicity results in the approach to use pentostatin in steroid-refractory aGvHD.[2]
Chronic graft-versus-host disease (GVHD) is the main cause of late morbidity and non–relapse mortality after hematopoietic stem cell transplantation (HSCT).
Most relevant to GVHD, Pentostatin causes marked reduction of CD4 and CD8 cells. There is also significant B-cell depletion with reduction of IgG levels.13 This should allow it to affect GVHD at the cellular level and thus has the potential to address the many manifestations of chronic GVHD. Pentostatin is found to be active in a phase 1 study in refractory acute GVHD. A phase 2 study of pentostatin in heavily pretreated patients (median age, 33 years; median of 4 prior regimens) with chronic GVHD showed a 55% objective response rate in 58 patients.
In comparison with other treatment options, pentostatin has some favourable characteristics and its effect is sustainable and the majority of responding patients survived. The costs for pentostatin are relatively low and the toxicity is moderate.
References:
[1]David A. Jacobsohn, Andrew L. Gilman, Alfred Rademaker et al. Evaluation of pentostatin in corticosteroid-refractory chronic graft-versus-host disease in children: a Pediatric Blood and Marrow Transplant Consortium study. BLOOD, 12 NOVEMBER 2009 _ VOLUME 114, NUMBER 20
[2] Stefan A. Klein1, Gesine Bug2, Sabine Mousset2 et al. Long term outcome of patients with steroid-refractory acute intestinal graft versus host disease after treatment with pentostatin. British Journal of Haematology, 154, 141–155

Pentostatin, Cyclophosphamide and Rituximab (PCR) Regimen.[Pubmed:28057947]

Hosp Pharm. 2016 Dec;51(11):888-893.

The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr., President, Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110-545, Arlington, VA 22203, email: OncRxSvc@comcast.net; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net. The information presented in this review is based on published data and clinical expertise and includes information not included in the product labeling. Incorporation of such published data provides a more robust assessment of the drugs and assists pharmacists in evaluation of orders for off-label use of these agents.

High-Dose Sirolimus and Immune-Selective Pentostatin plus Cyclophosphamide Conditioning Yields Stable Mixed Chimerism and Insufficient Graft-versus-Tumor Responses.[Pubmed:26071480]

Clin Cancer Res. 2015 Oct 1;21(19):4312-20.

PURPOSE: We hypothesized that lymphoid-selective host conditioning and subsequent adoptive transfer of sirolimus-resistant allogeneic T cells (T-Rapa), when combined with high-dose sirolimus drug therapy in vivo, would safely achieve antitumor effects while avoiding GVHD. EXPERIMENTAL DESIGN: Patients (n = 10) with metastatic renal cell carcinoma (RCC) were accrued because this disease is relatively refractory to high-dose conditioning yet may respond to high-dose sirolimus. A 21-day outpatient regimen of weekly Pentostatin (P; 4 mg/m(2)/dose) combined with daily, dose-adjusted cyclophosphamide (C;

Pentostatin, cyclophosphamide and rituximab for previously untreated advanced stage, low-grade B-cell lymphomas.[Pubmed:25828695]

Br J Haematol. 2015 Jun;169(6):814-23.

We conducted a prospective phase II trial of Pentostatin, cyclophosphamide and rituximab as initial therapy for patients with previously untreated advanced stage low-grade or indolent B-cell lymphomas (iNHLs). Of 83 evaluable patients, 91.6% attained an overall response and 86.8% a complete or unconfirmed complete response. The 3-year progression-free survival (PFS) and overall survival rates were 73% and 93%, respectively. The 3-year PFS rate was significantly different for different diagnoses (P = 0.01): 83% [95% confidence interval (CI): 0.72, 0.96] for follicular lymphomas, 73% (95% CI: 0.54, 1.0) for marginal zone lymphomas and 61% (95% CI: 0.46, 0.81) for small lymphocytic lymphomas. The most common adverse events were haematological. Of 509 cycles of chemotherapy administered, grade 3 or 4 neutropenia was reported in 68 cycles (13% of cycles administered) and most frequently occurred during cycles 4-6. This is the first report demonstrating the effectiveness of Pentostatin, cyclophosphamide and rituximab in patients with previously untreated iNHLs, including those over 60 years of age.