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What's New In Research - June 10, 2003
Graft versus host disease can be beneficial, as chronic disease improves outcome in multiple myeloma transplant cases.
Copyright 2003 Clinical Oncology Week via NewsRx.com

According to published research from Spain, "The outcome of 29 multiple myeloma patients receiving fludarabine and melphalan-based non-myeloablative allogeneic transplant (NMT) was evaluated.

"Event free survival (EFS) at 24 months was 33%, being significantly higher for patients who developed chronic graft-versus-host disease (cGVHD) when compared with those who did not [51% vs. 0% respectively, p=0.02; hazard rate=3.16 (95% CI=1.09-9.15, p=0.03)] as well as for patients transplanted in complete remission/partial response (CR/PR) or stable disease (SD), compared with those with refractory/progressive disease (43% vs. 0% respectively, p=0.02).

"Overall survival (OS) at 24 months was 60% [72% vs. 42% for patients who did and did not develop cGVHD respectively (p=0.1); 63% vs. 41% for patients in CR/PR or SD vs. refractory/progressive disease at transplant respectively (p=0.013)].

"At a median followup of 366 d, 13 patients remained in CR/PR (45% overall response rate). Nine patients have died, 3 of them as a result of disease progression and 6 (21%) as a result of transplant related mortality (TRM).

"Actuarial incidence of TRM was 37% for patients who developed acute GVHD vs. 13% for those who did not (log rank, p=0.04)," wrote J.A. Perez-Simon and colleagues.

The researchers concluded: "The present study suggests that graft-versus-myeloma effect is the main weapon for disease control after NMT in MM patients and the efficacy of this immune effect depends on tumor burden before transplant."

Perez-Simon and colleagues published their findings in British Journal of Haematology (Chronic but not acute graft-versus-host disease improves outcome in multiple myeloma patients after non-myeloablative allogeneic transplantation. Br J Haematol, 2003;121(1):104-108).

Additional information can be obtained by contacting J.A. Perez-Simon, Hospital Clinic University, Hematology Service, Paseo San Vicente S-N, Salamanca 37007, Spain.

Natco Unveils Cheap Bone Drug (launches Zoldonat at Rs2,800 per four mg injection against Rs13,000 an imported one)
Copyright (c) 2003 Informatics (India) Ltd.

Natco Pharma Ltd of Hyderabad has launched Zoldonat (Zoledronic Acid) for treatment of bone metastases for the first time in India. Zoldonat is the second product in the anti-cancer segment to be launched by Natco. Bone metastases is a natural side effect of cancers including lung, breast, prostrate, kidney, thyroid and multiple myeloma. Zoldonat is priced Rs2,800 per four-milligram (mg) injection against Rs13,000 for an imported one.

Cell adhesion-mediated drug resistance is associated with NF-kappa B activation.
Copyright 2003 Blood Weekly via NewsRx.com

"The microenvironment has been shown to influence tumor cell phenotype with respect to growth, metastasis, and response to chemotherapy. We have utilized oligonucleotide microarray analysis to identify signal transduction pathways and gene products altered by the interaction of myeloma tumor cells with the extracellular matrix component fibronectin that may contribute to the antiapoptotic phenotype conferred by the microenvironment. Genes with altered expression associated with fibronectin (FN) cell adhesion, either induced or repressed, were numerically ranked by fold change," scientists in the United States reported.

"FN adhesion repressed the expression of 469 gene products, while 53 genes with known coding sequences were induced by two-fold or more. Of these 53 genes with two-fold or greater increase in expression, 11 have been reported to be regulated by the nuclear factor-kappa B (NF-kappaB) family of transcription factors," said T.H. Landowski and colleagues, University of South Florida, College of Medicine.

"EMSA analysis demonstrated NF-kappaB binding activity significantly increased in cells adhered to fibronectin compared to cells in suspension. This DNA binding activity consisted primarily of RelB-p50 heterodimers, which was distinct from the NF-kappaB activation of TNF-alpha."

"These data demonstrate the selectivity of signal transduction from the microenvironment that may contribute to tumor cell resistance to programmed cell death," researchers concluded.

Landowski and colleagues published their study in Oncogene (Cell adhesion-mediated drug resistance (CAM-DR) is associated with activation of NF-kappa B (RelB/p50) in myeloma cells. Oncogene, 2003;22(16):2417-2421).

For more information, contact W.S. Dalton, University of South Florida, College of Medicine, H Lee Moffitt Cancer Center & Research Institute, Department Interdisciplinary Oncology, Tampa, FL 33612, USA.

Safety portions completed of two Phase I/II cancer trials of recombinant human lactoferrin with the Department of Hematology/Oncology at the Veterans Affairs Medical Center in Houston.
Copyright 2003 Gale Group Inc.

Agennix Inc., of Houston, said it completed the safety portions of two Phase I/II cancer trials of recombinant human lactoferrin with the Department of Hematology/Oncology at the Veterans Affairs Medical Center in Houston. The trials are in the U.S. and South America. Lactoferrin is a protein found naturally in milk and other exocrine secretions and is believed to play a role in the immune system. The trials are evaluating the product as a single agent for the treatment of solid tumors in patients who progressed on standard chemotherapy and whose tumors were not resectable. Thirty patients were enrolled in the safety phase. In the ongoing efficacy phase, an additional 38 patients will be treated with the highest doses. Complete results are expected later in the year.

AnorMED Inc., of Vancouver, British Columbia, has begun a second Phase II trial of AMD-3100 in multiple myeloma.
Copyright 2003 Gale Group Inc.

The study will examine AMD-3100 administered with G-CSF, the standard agent, and determine if the combination will mobilize the target number of stem cells required for transplantation in patients who have previously failed to mobilize an adequate number of cells. AMD-3100 is designed to block the CXCR4 chemokine receptor that is present on white blood cells and other immune cells.

High Dose Samarium -153 Edtmp (Ethylenediaminetetramethylene Phosphonic Acid) and Melphalan Chemotherapy with Peripheral Blood Stem Cell Rescue for Therapy of Patients with Multile Myeloma : Phase I and II Clinical Trial Preliminary Results
G. A. Wiseman*¹, A. Dispensieri², M. Q. Lacy², M. A. Gertz², ¹Radiology,
Mayo Clinic, Rochester, MN; ²Hematology - Internal Medicine, Mayo Clinic, Rochester, MN.

Objectives: Multiple myeloma is a malignant disease of plasma cells that is generally treated with high dose chemotherapy with or without radiation therapy. High dose therapy has been shown to result in longer survival than standard chemotherapy but requires marrow or peripheral blood stem cell rescue. Myeloma cells are radiosensitive but external beam radiation when used in high dose therapy results in additional toxicity without an improvement in outcome. Almost all patients with myeloma will relapse even after high dose therapy and will die from the disease. The objective of our study was to determine the safety and efficacy of using a high dose of a bone seeking therapeutic radiopharmaceutical added to Melphalan chemotherapy to treat patients with multiple myeloma

Methods: We have completed a phase I and phase II trial of combining high dose Sm-153 EDTMP (Quadramet®) with Melphalan 200mg/m² IV for treatment of multiple myeloma in 52 patients with symptomatic disease. The phase I trial showed the optimal dosing to be 4000 cGy absorbed dose to the red marrow calculated from a trace dose of Sm-153 EDTMP given one week prior to the therapy dose. The 4000 cGy dose to red marrow dosing was used for the phase II trial and was given 10 days prior to Melphalan and 11 days prior to stem cell infusion.

Results: Toxicity from the targeted radioisotope therapy was only mild transient nausea or vomiting occurring 1-3 days after the Sm-153 EDTMP therapy infusion. No renal, bladder or neurologic toxicity were seen and all patients had normal engraftment. Preliminary analysis of the response data using International Workshop Response Criteria shows in the first 21 patients there was a 95% overall response rate with a 29% complete response rate and a 29% very good partial response rate.

Conclusions: Sm-153 EDTMP can be administered safely at doses of 4000 cGy to the red marrow with only mild transient GI symptoms. This high dose bone targeted radioisotope treatment can be used along with Melphalan chemotherapy to treat patients with multiple myeloma and shows high therapeutic response rates.

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