mesna and Lymphoma

Many investigators have reported the dose and schedule of VP-16 administration, but as yet they remain undetermined. VP-16 is one of the most active agents for several carcinomas and usually administered intravenously over 3 to 5 consecutive days in combination with other agents. Although, the development of new drugs recently reduces the use of VP-16 administration, VP-16 is still an important drug for the treatment of lung cancer and malignant lymphoma. In this paper, the combination therapy with VP-16, especially in the treatment of lung cancer and malignant lymphoma, are reviewed.

Topics: Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Small Cell; Cisplatin; Clinical Trials, Phase II as Topic; Cytarabine; Etoposide; Humans; Ifosfamide; Lung Neoplasms; Lymphoma; Mesna; Methylprednisolone; Mitoxantrone

To evaluate the long-term outcome of dose density chemotherapy in the treatment of aggressive lymphoma, we analyzed 142 patients with untreated aggressive lymphoma. Chemotherapy was an eight-drug regimen given in weekly intervals in two prospective trials. The median observation period was 8 years; the longest follow-up was 13 years. Overall survival at 8 years was 0.583. The 8-year survival of patients < or =60 years was significantly better than that of older patients, namely 0.713 vs 0.304 (p=0.000000697). This excellent survival of patients aged < or =60 years was identical for high-risk and high-intermediate-risk patients compared with low-risk and low-intermediate-risk patients in the age-adjusted international prognostic index (IPI). The excellent long-term results of the CEOP/IMVP-Dexa regimen (cyclophosphamide, epirubicin, vincristine, and prednisone/ifosfamide with systemic mesna, methotrexate, etoposide, and dexamethasone) for patients aged < or =60 years suggest that this regimen might be superior to the standard CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisolone) and needs to be tested in comparison to high-dose regimens and novel approaches including antibody treatment.

Topics: Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Cause of Death; Cyclophosphamide; Dexamethasone; Epirubicin; Etoposide; Humans; Ifosfamide; Longitudinal Studies; Lymphoma; Mesna; Methotrexate; Middle Aged; Prednisone; Survival Analysis; Treatment Failure; Treatment Outcome; Vincristine

Treatment with the anti-CD20 antibody rituximab prior to stem cell collection may lead to tumor-free stem cell collections in patients with B-cell lymphoma undergoing autologous stem cell transplantation. To test the feasibility of obtaining polymerase chain reaction (PCR)-negative stem cell collection, 30 patients with a variety of B-cell lymphomas were enrolled in a protocol employing a common MINE (mitoxantrone/ifosfamide/etoposide) salvage regimen with rituximab (in vivo purging). Rituximab 400 mg/m2 was administered weekly for 3 weeks on days 1, 6, and 8 in relation to the last MINE cycle, which was followed by growth factor-stimulated peripheral stem cell collection. The median number of CD34(+) cells/kg was 2.5 million cells/kg collected over a median of 5 days. Polymerase chain reaction amplification for the t (14;18) or the heavy-chain gene rearrangement was performed prior to treatment and on the leukapheresis sample. Out of 15 patients who had a positive PCR signal prior to treatment, 10 had PCR-negative stem cell collections, whereas 5 had PCR-positive stem cell collections. After high-dose chemotherapy and stem cell transplant, all patients with a PCR-positive signal pretreatment became PCR negative. We conclude that rituximab may increase the yield of tumor-free stem cells. Higher rates of PCR negativity have been reported when more intense and protracted chemoimmunotherapy regimens have been employed. The magnitude of clinical benefit and the significance of the PCR analysis in stem cells after rituximab requires larger studies.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antigens, CD20; Antigens, CD34; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Etoposide; Female; Humans; Ifosfamide; Lymphoma; Lymphoma, Non-Hodgkin; Male; Mesna; Middle Aged; Mitoxantrone; Polymerase Chain Reaction; Recurrence; Remission Induction; Rituximab; Salvage Therapy; Stem Cells; Time Factors

Treatment of early relapsing or resistant non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) remains problematic. High-dose chemotherapy followed by autologous peripheral blood stem cell (PBSC) transplantation improves the prognosis for patients in response following standard dose regimens. We adopted the strategy of using salvage chemotherapy to debulk disease and simultaneously mobilize stem cells. We used regimens based on ifosfamide and etoposide because these drugs are not usually used as the front-line treatment. Twenty-seven patients with NHL received MINE chemotherapy (mesna and ifosfamide 1330 mg/m2 and etoposide 65 mg/m2 i.v. days 1-3, and mitoxantrone 8 mg/m2 i.v. day 1). The same schedule, but higher doses were used for PBSC stimulation (mesna, ifosfamide 1700 mg/m2, etoposide 175 mg/m2, mitoxantrone 10 mg/m2). Forty-six patients with HD received VIM chemotherapy (mesna, ifosfamide 1200 mg/m2 i.v. days 1-5, etoposide 90 mg/m2 i.v. days 1, 3, and 5, methotrexate 30 mg/m2 i.v. days 1 and 5). After both VIM and high dose MINE, chemotherapy for mobilization was followed by G-CSF administered at a dose 5-16 micrograms/kg/day depending on the clinicians judgement of the patient's pretreatment. Complete response after VIM and MINE were 39% and 38%, respectively; partial response (PR) rates were 17% and 29%, and stable disease (SD) 25% and 4%, respectively. In both groups, patients with relapsing disease had better responses than did those with primary progressive disease. Both regimens exhibited excellent mobilizing capacity. We performed 213 aphereses with a median 3 per patient starting on either day 13 as a median for VIM, or on day 12 as a median for MINE. In the majority of patients, the collection started in the time interval median +/- 1 day (n = 62, 85%). The median yields were 10.6 x 10(6) CD34+ cells/kg and 53.1 x 10(4) CFU-GM/kg for VIM, and 13.3 x 10(6) CD34+ cells/kg and 54.5 x 10(4) CFU-GM/kg for MINE. We collected at least 2.5 x 10(6) CD34+ cells/kg in all but six patients (8%), and the harvested amount of CD34+ cells was less than 1.0 x 10(6)/kg in only two patients (3%). The toxicity of VIM and MINE was minimal and chemotherapy-induced trombocytopenia did not occur with PBSC collection.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Etoposide; Female; Graft Survival; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Ifosfamide; Kinetics; Lymphoma; Male; Mesna; Methotrexate; Middle Aged; Mitoxantrone; Prognosis; Salvage Therapy; Treatment Outcome

We have previously reported that combination chemotherapy based on the drugs cytarabine/platinum is effective in recurring lymphomas. In this phase II study, we prospectively studied a combination regimen of mesna/ifosfamide, mitoxantrone and etoposide (MINE) in patients with recurring lymphoma who had already received cytarabine/platinum but did not respond to the treatment.. 48 patients received MINE at the following doses: mesna 1.33 g/m2 i.v. daily x 3, and 500 mg p.o. daily 4 hours after each i.v. dose; ifosfamide 1.33 g/m2 i.v. daily, given concurrently with mesna, x 3 d; mitoxantrone 8 mg/m2 i.v. on day 1; and etoposide 65 mg/m2 i.v. daily x 3. Treatment cycles were 21-28 days apart, depending on patients' blood counts, with a maximum number of 6 cycles in responding patients. The histologic grade of the lymphomas according to the Working Formulation was low in 8 patients and intermediate in 40 patients. In the latter group, 12 were transformed from low grade.. Overall, 48% of the patients responded, with 21% having a complete response (CR), and 27% having a partial response (PR). The median survival time was 9 months, and the median follow-up of survivors is 51 months at this writing. Median time to treatment failure was 12 months for patients with complete responses, and 5 months for patients with partial responses. The most serious complication was myelosuppression, with 2 deaths resulting from neutropenic infection.. The MINE regimen induced responses in a moderate fraction of patients after their prior exposure to cytarabine/platinum salvage therapy, indicating there is no absolute cross resistance between these drug regimens.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Etoposide; Female; Humans; Ifosfamide; Lymphoma; Male; Mesna; Middle Aged; Mitoxantrone; Platinum; Prospective Studies; Recurrence; Remission Induction; Salvage Therapy; Survival Rate; Treatment Failure

To evaluate the response to oral Etoposide when combined with mesna, ifosfamide, and mitoxantrone in patients with relapsed and/or refractory lymphoma. To evaluate response and its duration after administration of intravenous Etoposide, methylprednisolone, high-dose cytosine arabinoside, and cisplatin (ESHAP) as consolidation therapy after complete or partial responses (CR or PR, respectively) or after crossover therapy for progressive disease.. Patients received MINE(o) consisting of mesna, 1.33 g/m2 infused over 1 hour daily x 3 followed 4 hours later by oral mesna at 500 mg; ifosfamide, 1.33 g/m2 infused over 1 hour daily x 3; mitoxantrone, 8 mg/m2 intravenously on day 1, and oral VP-16, 30 mg/m2 daily x 13. The ESHAP regimen consisted of intravenous VP-16, 40 mg/m2 infused over 2 hours daily x 4; methylprednisolone, 500 mg intravenously daily x 4; cytosine arabinoside, 1.5 g/m2 infused over 3 hours on day 4; and cisplatin, 25 mg/m2 given as a continuous 24-hour infusion daily x 4. Statistical analysis was performed using the 2-stage design described by Simon. For the oral VP-16 regimen to be of interest, at least 36% patients had to achieve a complete remission.. The overall response rate achieved with MINE(o) was 40% (15% CR, 25% PR). Seven patients with prior exposure to cytosine arabinoside and cisplatin (AP) received MINE(o) alone of whom only one achieved a response (CR). Thirteen patients without prior exposure to AP received consolidation (2 patients) or crossover (11 patients) therapy with ESHAP. Crossover therapy with ESHAP further improved the response in only two of five patients with partial response to MINE(o) and none of six patients who failed MINE(o). Median response duration for the patients who received MINE(o)/ESHAP was 12 weeks (range, 4-55 weeks).. Oral VP-16 combined with ifosfamide/mesna and mitoxantrone at the doses and schedules indicated has little activity against relapsed and/or refractory lymphomas. Crossover therapy with ESHAP did not further improve the response rate. The duration of response after MINE(o)/ESHAP was short.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cross-Over Studies; Cytarabine; Etoposide; Female; Humans; Ifosfamide; Lymphoma; Male; Mesna; Methylprednisolone; Methylprednisolone Hemisuccinate; Middle Aged; Mitoxantrone; Prednisone; Salvage Therapy

Sterile haemorrhagic cystitis (SHC) is a possible side effect of cyclophosphamide which can severely impact quality of life. Mesna and diuresis are effective in human medicine to prevent SHC. The aim of the present study was to compare the efficacy of mesna versus diuresis with furosemide in preventing SHC in dogs treated with cyclophosphamide within a multidrug chemotherapy induction protocol for malignant lymphoma. Medical records of dogs treated at the Clinic of Small Animal Medicine, Munich, between 1997 and 2009 were analysed retrospectively. Of the 131 dogs included, 33 received no prophylaxis (group 1), 43 received mesna (group 2), and 55 received furosemide (group 3). Age, gender, breed, bodyweight, body surface area, dose and application method of cyclophosphamide, and the method of SHC prophylaxis were compared between dogs with and without SHC. Six dogs (4.6 per cent) developed SHC. The incidence of SHC in groups 1, 2 and 3 was 4/33 (12.1 per cent), 1/43 (2.3 per cent), and 1/55 (1.8 per cent), respectively. Dogs receiving either mesna or furosemide were significantly less likely to develop SHC (P=0.03). Otherwise no significant differences were found. In conclusion, this study demonstrates the efficacy and the medical indication of mesna and furosemide for prevention of cyclophosphamide-induced SHC.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cystitis; Diuretics; Dog Diseases; Dogs; Female; Furosemide; Hemorrhage; Lymphoma; Male; Mesna; Protective Agents; Retrospective Studies; Risk Factors; Treatment Outcome

ICE/R-ICE (ifosfamide, carboplatin, and etoposide without or with rituximab) chemotherapy followed by autologous stem cell transplantation is an established regimen in refractory/relapsed lymphoma. Few studies have addressed which factors are important in determining peripheral blood stem cell (PBSC) mobilization efficiency or nonmobilization following ICE/R-ICE. Between 2004 and 2013, 88 patients with refractory/relapsed lymphoma who received ICE/R-ICE salvage-chemotherapy prior to granulocyte colony stimulating factor (G-CSF) stimulated PBSC mobilization at a single center were identified. Mobilization efficiency was assessed by time from ICE/R-ICE to day of harvest, duration of G-CSF use, days to peripheral blood (PB) CD34(+) ≥15/µL, PB CD34(+) number on harvest day, CD34(+) yield and nonmobilization rate. Median PB CD34(+) at harvest were 54/μL (7-524); median days to first apheresis was 15 (11-30); median harvested total CD34(+) were 5.46 × 10(6) /kg (0.96-44.36); 71 patients (80.7%) successfully mobilized; 20 (22.7%) patients were poor mobilizers; 14 (15.9%) patients were considered nonmobilizers with maximal PB CD34(+) <7/µL and did not proceed to apheresis. Six of 20 poor mobilizers were apheresed with PB CD34(+) 7-12/µL, 50% were successfully harvested. No differences were found between ICE and R-ICE regimens. Impaired mobilization efficiency was associated with age, remission status, >1 line of induction chemotherapy, four cycles ICE/R-ICE and grade 4 neutropenia. Prior bone marrow (BM) involvement was associated with nonmobilization. The majority of patients can be successfully mobilized with ICE/R-ICE. Prior BM involvement is associated with high rates of nonmobilization following ICE/R-ICE. Such patients may benefit from novel mobilization agents and/or alternative salvage regimens to ICE/R-ICE.

Topics: Adult; Aged; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Blood Cell Count; Carboplatin; Combined Modality Therapy; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Ifosfamide; Lymphoma; Male; Mesna; Middle Aged; Retrospective Studies; Rituximab; Salvage Therapy; Transplantation, Autologous; Young Adult

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

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cytarabine; Etoposide; Humans; Ifosfamide; Lymphoma; Mesna; Methylprednisolone Hemisuccinate; Mitoxantrone; Neoplasm Recurrence, Local; Salvage Therapy; Survival Rate

Topics: Drug Therapy, Combination; Humans; Ifosfamide; Lymphoma; Mesna; Urologic Diseases

With the intent of using active regimens in the front-line setting, new combinations of chemotherapy have been tested as salvage treatment in lymphoma patients at M.D. Anderson Hospital. Combinations based on ifosfamide plus etoposide, including IMVP-16 (ifosfamide/methotrexate/etoposide) and MIME (methyl-GAG/ifosfamide/methotrexate/etoposide) resulted in overall and complete responses (CRs) of 60 and 25%, respectively. Long-term follow-up of MIME indicates a 25% cure rate in intermediate-grade lymphoma patients who achieve CR. The in vitro synergism of platinum and high-dose cytarabine recently has been confirmed clinically. A study is currently under way to evaluate the effect of integrating MINE (mesna/ifosfamide/mitoxantrone/etoposide) and ESHAP (etoposide/methyl prednisolone/cytarabine/platinum) into one protocol.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cytarabine; Drug Evaluation; Etoposide; Follow-Up Studies; Humans; Ifosfamide; Lymphoma; Lymphoma, Non-Hodgkin; Mesna; Methotrexate; Methylprednisolone; Methylprednisolone Hemisuccinate; Mitoguazone; Mitoxantrone; Remission Induction; Survival Rate

Ifosfamide was given to 61 patients with malignant solid tumors diagnosed before the age of 21 years. In this phase II study, all patients received 1.6 g/m2/day X 5 iv over 15 minutes followed by mesna at a dose of 400 mg/m2 iv at 15 minutes and 4 and 6 hours after ifosfamide. Responses were observed in five of 15 patients with osteosarcoma, two of ten with neuroblastoma, two of six with Wilms' tumor, two of five with rhabdomyosarcoma, four of eight with other soft tissue sarcomas, one of one with retinoblastoma, one of two with germ cell tumors, one of one with B-cell lymphoma, and one of one with a primitive neuroectodermal tumor. Fifty-nine of 61 patients had received prior alkylating agent therapy which included cyclophosphamide, cisplatin, mechlorethamine, melphalan, or dacarbazine. Fourteen of 19 responses developed in patients whose tumors were resistant to treatment with cyclophosphamide. A patient with malignant Schwannoma who had received no prior chemotherapy developed a complete response which lasted 12 months. A patient with brain metastases of osteosarcoma has had complete response for greater than 2 years. Complete response was also observed in a patient with B-cell lymphoma. Toxicity consisted of mild to moderate nausea and vomiting, transient reversible myelosuppression, occasional elevation of serum BUN or creatinine, and transient neurotoxicity characterized by somnolence, confusion, weakness, tremor, hallucinations, or seizures. We conclude that ifosfamide is an important alkylating agent without apparent complete cross-resistance with cyclophosphamide, and as such should be further investigated for determination of its activity in patients with pediatric neoplasms and considered for incorporation into phase II-III trials for certain tumors.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Drug Evaluation; Female; Hematologic Diseases; Humans; Ifosfamide; Infant; Lymphoma; Male; Mesna; Neoplasms; Nervous System Diseases; Neurilemmoma; Osteosarcoma; Urologic Diseases