mesna and Multiple-Myeloma

Difficulties associated with current intensive induction regimens for multiple myeloma and uncertainty as to how to achieve optimal peripheral blood progenitor cell mobilisation (PBPC) prompted this study of an oral induction regimen, Z-Dex (oral idarubicin and dexamethasone) followed by PBPC mobilisation using four different regimens. Thirty-patients received Z-Dex (median age 56 years, range 46-66 years) including 24 patients with previously untreated disease. The overall response rate was 75% with a CR rate of 16.7% and PR rate of 75.7% in patients with previously untreated disease. We compared four mobilisation regimens: low-dose (LD) cyclophosphamide, high-dose (HD) cyclophosphamide, cis-platin/VP16 and cis-platin, Ara-C and dexamethasone (DHAP). Failure to mobilise optimal numbers of PBPCs (>1.0 x 10(6) CD34+ cells/kg and >20 x 10(4) CFU-GM/kg) was seen in two patients who received LD cyclophosphamide, in two patients who received HD cyclophosphamide and three patients who received cis-platin/VP16. No patient failed to mobilise adequate numbers of PBPCs following DHAP. In previously untreated patients, DHAP mobilised significantly more PBPC than LD cyclophosphamide (P=0.02), HD cyclophosphamide (P=0.0015) and cis-platin/VP16 (P=0.021). This study demonstrates the efficacy of Z-Dex in inducing tumour responses in patients with multiple myeloma without limiting PBPC mobilisation in subsequent dose-intensive schedules. Furthermore, we also demonstrate that DHAP is superior to cyclophosphamide (low- and high-dose) and cis-platin/VP16 in mobilising PBPCs and demonstrated a degree of tumour control.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Colony-Forming Units Assay; Cyclophosphamide; Cytarabine; Dexamethasone; Dose-Response Relationship, Drug; Etoposide; Female; Flow Cytometry; Hematopoietic Stem Cell Mobilization; Humans; Idarubicin; Male; Mesna; Middle Aged; Multiple Myeloma; Remission Induction

Topics: Atrial Fibrillation; Cyclophosphamide; Drug Therapy, Combination; Hematopoietic Stem Cell Mobilization; Humans; Male; Mesna; Middle Aged; Multiple Myeloma

The purpose of this report is to summarize information on drugs recently approved by the U.S. Food and Drug Administration. Three drugs have recently been approved: Gleevec (imatinib mesylate) at a starting dose of 400 or 600 mg daily for the treatment of malignant unresectable and/or metastatic gastrointestinal stromal tumors; Mesnex (mesna) tablets as a prophylactic agent to reduce the incidence of ifosfamide-induced hemorrhagic cystitis, and Zometa (zoledronic acid) for the treatment of patients with multiple myeloma and for patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Prostate cancer should have progressed after treatment with at least one hormonal therapy. The recommended dose and schedule is 4 mg infused over 15 minutes every 3-4 weeks. These three drugs represent three different types of drug approval: Gleevec is an accelerated approval and supplemental new drug application (NDA); Mesnex tablets represent an oral formulation of a drug approved 14 years ago as an intravenous formulation, and Zometa represents a standard NDA for a noncytotoxic, supportive-care drug. Information provided includes rationale for drug development, study design, efficacy and safety results, and pertinent literature references.

Topics: Antineoplastic Agents; Antineoplastic Agents, Alkylating; Benzamides; Bone Neoplasms; Cystitis; Diphosphonates; Drug Approval; Gastrointestinal Neoplasms; Hematuria; Hemorrhage; Humans; Ifosfamide; Imatinib Mesylate; Imidazoles; Mesna; Multiple Myeloma; Orphan Drug Production; Piperazines; Protective Agents; Pyrimidines; Randomized Controlled Trials as Topic; United States; United States Food and Drug Administration; Zoledronic Acid

We report a 69-year-old man who suffered an extraosseous tumor of immunoglobulin D myeloma (lambda type) in the shoulder girdle, mimicking a primary soft tissue sarcoma. The tumor was isointense with adjacent muscle on T1-weighted MR images, and hyperintense on T2-weighted images. No continuity with the neighboring bone was noted. After administration of gadolinium, the central part of the tumor showed marked contrast enhancement. Although the tumor showed a complete response to the initial chemotherapy, the patient died of the disease 31 months after its initial manifestation. Several bone marrow aspirations and biopsies of the ilium and sternum had shown no increase in plasma cells (range 0.6-1.2%) until the disease became advanced 19 months after its initial manifestation.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Dacarbazine; Doxorubicin; Humans; Ifosfamide; Immunoglobulin D; Immunoglobulin lambda-Chains; Magnetic Resonance Imaging; Male; Mesna; Multiple Myeloma; Shoulder; Soft Tissue Neoplasms

Peripheral blood progenitor cells are being used increasingly as part of the treatment protocol for a variety of haematological malignancies. The most appropriate mobilisation therapy and the optimum collection procedures have yet to be fully elucidated. 28 patients with myeloma (9), NHL (11) and HD (8) underwent PBSC mobilisation and harvesting between November 1992 and October 1993. Two protocols were used; the myeloma group received high-dose cyclophosphamide, 7 g/m2 + G-CSF and were leucapheresed on 5 consecutive days during the recovery period using the Haemonetics V50 and the lymphoma group a lower dose of cyclophosphamide, 3 g/m2 + G-CSF followed by leucapheresis on 2 or 3 occasions using a Cobe Spectra. Median time to achieve a WBC of 1 x 10(9)/l during the recovery phase, was 14 days (11-16) and 10 days (9-15) respectively. Median numbers of MNC and CFU-GM collected for the myeloma group were 5.9 x 10(8)/kg (2.5-13.5) and 69.4 x 10(4)/kg (9.9-268.1) and for the lymphoma group. 5.1 x 10(8)/kg (1.2-11.1) and 35.4 x 10(4)/kg (1.2-129.7). Three patients with lymphoma had a low yield of CFU-GM, two of which did not proceed to autograft. The third patient failed to engraft and died despite receiving bone marrow backup. For the remaining 25 patients, median time to neuts > 0.5 x 10(9)/l and platelets > 50 x 10(9)/l was 9 (8-13) and 11 (9-23) days for the myeloma group and 12 (9-15) and 13 (9-180) days for the lymphomas. We found a strong correlation between CD34+ cells and CFU-GM from the last 9 patients. There is a correlation between CFU-GM infused and speed of engraftment. All patients who received > 10 x 10(4) CFU-GM/kg showed a rapid engraftment for neutrophils and platelets. In all cases, when > 4 x 10(8)/kg MNC were harvested, > 10 x 10(4) CFU-GM/kg were obtained. Sufficient cells for a rapid engraftment can be obtained from 2 leucaphereses in the majority of patients. The recovering peripheral blood WBC provides a good indicator of when to harvest. The target value of CFU-GM can be predicted by the number of cells harvested and by the number of CD34 positive cells in the leucapheresis product.

Topics: Aged; Antigens, CD34; Antineoplastic Combined Chemotherapy Protocols; Blood Component Removal; Bone Marrow Transplantation; Cohort Studies; Colony-Forming Units Assay; Combined Modality Therapy; Cyclophosphamide; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Lymphoma; Mesna; Middle Aged; Multiple Myeloma; Recombinant Proteins