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Journal of Cancer Research and Clinical... 1998Secondary acute myeloid leukemia (s-AML) and secondary myelodysplastic syndrome (s-MDS) probably represent the worst possible long-term complications of cancer therapy... (Review)
Review
Risk of secondary myeloid leukemia and myelodysplastic syndrome following standard-dose chemotherapy or high-dose chemotherapy with stem cell support in patients with potentially curable malignancies.
Secondary acute myeloid leukemia (s-AML) and secondary myelodysplastic syndrome (s-MDS) probably represent the worst possible long-term complications of cancer therapy in patients originally cured of their primary malignancy. The frequency and type of s-AML and s-MDS are reviewed for patients treated with standard and/or high-dose chemotherapy for Hodgkin's disease, non-Hodgkin's lymphoma (NHL), and breast or testicular cancer. Patients treated for Hodgkin's disease, have a 20- to 40-fold increased risk of developing s-AML, this risk increasing with the number of mechlorethamine-containing cycles given as well as following splenectomy and in patients more than 40-50 years of age. Generally, patients with NHL, breast or testicular cancer experience a lower, 2- to 15-fold, risk of developing s-AML. Epipodophyllotoxins appear to be the most important factor for s-AML in patients treated for testicular cancer. Doses of 2g/m2 or more are associated with an increased risk of s-AML and, with these high doses, a cumulative incidence of 2% 3% at 5 years is observed. Adjuvant cyclophosphomide, methobrexate, 5-Fu therapy in breast cancer patients does not appear to increase risk significantly as compared to the general population. The extent of the leukemogenic potential of anthracyclines remains to be defined. NHL patients receiving mechlorethamine, prednimustine or long-term maintenance therapy are also at an increased risk of s-AML. A considerably increased risk of developing AML, with a cumulative incidence of approximately 9% at 5 years, has been observed following allogenic bone marrow transplantation (ABMT) or peripheral stem cell transplantation (PBSCT) in patients with NHL. It is likely that the increased risk of s-AML/s-MDS following high-dose chemotherapy with ABMT or PBSCT is related to prior treatment rather than to high-dose chemotherapy itself. However, this issue remains to be conclusively addressed. s-AML or s-MDS rarely develops after allogenic bone marrow transplantation. s-AML and s-MDS increasingly represent a problem in modern cancer therapy because of better treatment strategies, which result in improved cure rates. Patients who receive chemotherapy must be informed about the potential risk of developing s-AML or s-MDS. Future studies should include a follow-up long enough to record the occurrence of all s-AML/s-MDS and all potential influencing factors reliably. These data would enable risk factors to be defined and risk/benefit analyses to be carried out, allowing the correct assessment of current and future therapy strategies.
Topics: Acute Disease; Antineoplastic Agents; Combined Modality Therapy; Dose-Response Relationship, Drug; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid; Myelodysplastic Syndromes; Neoplasms; Neoplasms, Second Primary
PubMed: 9619748
DOI: 10.1007/s004320050156 -
Neurologia (Barcelona, Spain) Mar 1998
Review
Topics: Aged; Antineoplastic Agents, Alkylating; Epilepsies, Myoclonic; Humans; Male; Prednimustine
PubMed: 9608225
DOI: No ID Found -
Journal of Clinical Oncology : Official... May 1998To compare mantle-cell lymphomas (MCLs) and follicle-center lymphomas (FCLs) for their features of clinical presentation, response to chemotherapy, and prognosis on the... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Mantle-cell lymphomas have more widespread disease and a slower response to chemotherapy compared with follicle-center lymphomas: results of a prospective comparative analysis of the German Low-Grade Lymphoma Study Group.
PURPOSE
To compare mantle-cell lymphomas (MCLs) and follicle-center lymphomas (FCLs) for their features of clinical presentation, response to chemotherapy, and prognosis on the basis of a prospective randomized clinical trial.
PATIENTS AND METHODS
Patients with MCL and FCL who entered onto the prospective randomized comparison of cyclophosphamide, vincristine, and prednisone (COP) versus prednimustine and mitoxantrone (PmM) followed by a second randomization for interferon (IFN) maintenance versus observation only.
RESULTS
One hundred sixty-five of 234 patients had FCL and 45 of 234 patients had MCL. With FCL, both sexes were equally affected (men, 47%); patients with MCL were predominantly men (78%; P < .0004) and had a higher median age (64 v 53 years; P < .0001). Patients with MCL also had more widespread disease, reflected by the proportion of patients with two or greater extranodal manifestations (43% v 21%; P < .005) and nine or greater involved nodal areas (64% v 45%; nonsignificant [NS]). Response to chemotherapy was significantly lower in patients with MCL (complete remission [CR] + partial remission [PR], 69% v 88%; P < .05) and occurred at a slower pace. Patients with MCL also had a shorter event-free interval (median, 8 v 24 months; P < .0001) and overall survival (median, 28 v 77 months; P < .0001). In both subtypes, however, patients with less than two residual lymphoma manifestations in remission experienced a relatively good prognosis with an estimated 5-year survival of greater than 60% for MCL and greater than 75% for FCL.
CONCLUSION
MCL and FCL differ substantially in their features of presentation, response to chemotherapy, and long-term prognosis. The extent of residual disease after completion of chemotherapy discriminates patients with different prognosis and may be used for the stratification of postremission strategies.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Disease-Free Survival; Female; Humans; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Male; Middle Aged; Mitoxantrone; Prednimustine; Prednisone; Prospective Studies; Survival Rate; Vincristine
PubMed: 9586911
DOI: 10.1200/JCO.1998.16.5.1922 -
Haematologica Jan 1998The evolution of Waldenström's macroglobulinemia (WM) into chronic or acute myeloid leukemia (AML) is a rare event. Most of these cases have occurred after treatment... (Review)
Review
The evolution of Waldenström's macroglobulinemia (WM) into chronic or acute myeloid leukemia (AML) is a rare event. Most of these cases have occurred after treatment with alkylating agents. We herein report a case of WM terminating in an acute myelomonocytic leukemia after treatment with prednimustine and chlorambucil and present a review of the literature.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Leukemia, Myelomonocytic, Acute; Male; Middle Aged; Waldenstrom Macroglobulinemia
PubMed: 9542328
DOI: No ID Found -
Oncology (Williston Park, N.Y.) Sep 1997Between 1989 and 1993, 409 evaluable patients with breast cancer have been treated with tegafur and uracil (UFT) in an adjuvant setting in two different trials. Data... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Between 1989 and 1993, 409 evaluable patients with breast cancer have been treated with tegafur and uracil (UFT) in an adjuvant setting in two different trials. Data from both trials were reviewed in December 1995 after a mean follow-up of 5.09 +/- 1.1 years (range, 2.9 to 7.1 years). The aim of the first trial was to demonstrate the activity of UFT 400 mg/day for 6 months plus prednimustine 60 mg/m2 for 7 consecutive days, every 28 days in 6 cycles given orally (arm B). This scheme was compared with 6 cycles of cyclophosphamide 600 mg/m2, plus methotrexate 40 mg/m2, plus fluorouracil 600 mg/m2, every 4 weeks (arm A). In this study, 187 premenopausal women were evaluable, 96 in arm A and 91 in arm B, all of whom had positive axillary nodes. Although there were more younger patients in arm A than in arm B, prognostic factors were similar in both groups. Disease-free survival and overall survival were similar in both arms. However, some concern is raised by the low disease-free survival rate. The toxicity was mild (mainly nausea and vomiting and alopecia) and slightly worse in arm A. We believe that oral administration could be a useful alternative to the parenteral route. In the second trial, 222 evaluable patients received 20 mg/day of tamoxifen (Nolvadex) for 1 year (arm A), or the same dose of tamoxifen plus UFT 400 mg/day for 6 months. All patients were postmenopausal, and the characteristics of the tumors were the same as those in patients in the first trial. In arm A there were 109 patients and in arm B, 113. The groups were well balanced. The overall survival and the disease-free survival rates were equal in both arms, but were longer in arm B in the subset of patients with five or more axillary-involved nodes. The toxicity was negligible in both arms. We conclude that UFT/tamoxifen might be useful in postmenopausal patients with five or more involved nodes who are unable to follow a more aggressive schedule because of their age or low performance status.
Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Drug Combinations; Female; Fluorouracil; Humans; Methotrexate; Middle Aged; Postmenopause; Prednimustine; Premenopause; Spain; Survival Analysis; Tamoxifen; Tegafur; Uracil
PubMed: 9348574
DOI: No ID Found -
Journal of Clinical Oncology : Official... Jan 1998We report the results of a randomized study of the European Organization for Research and Treatment of Cancer (EORTC) Lymphoma Group, which compared a chemotherapy... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
CHOP is the standard regimen in patients > or = 70 years of age with intermediate-grade and high-grade non-Hodgkin's lymphoma: results of a randomized study of the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Study Group.
PURPOSE
We report the results of a randomized study of the European Organization for Research and Treatment of Cancer (EORTC) Lymphoma Group, which compared a chemotherapy regimen specifically devised for elderly patients, ie, etoposide, mitoxantrone, and prednimustine (VMP), versus the standard regimen of cyclophosphamide, doxorobucin, vincristine, and prednisone (CHOP) in patients older than 70 years of age with intermediate- and high-grade non-Hodgkin's lymphoma (NHL).
PATIENTS AND METHODS
Patients older than 70 years of age with stage II, III, or IV intermediate- and high-grade NHL, with an Eastern Cooperative Oncology Group (ECOG) performance status less than 4 and acceptable cardiac, renal, and liver function were randomized to receive six courses of VMP or six courses of CHOP. Between February 1989 and June 1994, 130 patients aged 70 to 93 years (median, 75) were enrolled and 120 were assessable for response, 60 patients in each arm.
RESULTS
Overall objective response rates were 50% and 77% in VMP- and CHOP-treated patients, respectively (P = .01), while complete response (CR) rates were borderline significant (27% v 45%; P = .06). At 2 years, the progression-free survival (PFS) rate was 25% with VMP versus 55% with CHOP (P = .002) and the overall survival (OS) rate was 30% with VMP versus 65% with CHOP (P = .004). Statistically significant more alopecia and neurologic and gastrointestinal toxicities were reported with CHOP.
CONCLUSION
CHOP is the standard regimen for patients > or = 70 years of age with stage II to IV intermediate- and high-grade NHL.
Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Etoposide; Humans; Lymphoma, Non-Hodgkin; Mitoxantrone; Prednimustine; Prednisone; Vincristine
PubMed: 9440719
DOI: 10.1200/JCO.1998.16.1.27 -
Leukemia Apr 1997We evaluated 1179 consecutive patients with low-grade B-NHL diagnosed according to criteria of the Kiel classification and presenting with initial bone marrow...
We evaluated 1179 consecutive patients with low-grade B-NHL diagnosed according to criteria of the Kiel classification and presenting with initial bone marrow involvement. Therapeutic approaches were not changed during the observation period 1975-1995. CLL (n=895) and IC (n=169) were treated palliatively with chlorambucil/prednisone or prednimustine. In CBCC (n=65) and CC (n=50) remission was induced with COP or CHOP. The overall response rate was 67%, but only 35% of CBCC and 23% of CC patients achieved complete remission. Median survival was 64 months in CBCC and 28 months in CC. As the median age of our patient population was 68 years (range: 23-93) it seems doubtful whether overall prognosis can be improved by aggressive therapeutic measures. One exception might be CBCC patients who were younger (median age 56 years) and who were usually in good general condition so that they might qualify for high dosage chemotherapy and stem cell support. Whether the prognosis of IC and CLL (median survival 74 months and 107 months, respectively) can be improved by treatment with drugs such as purine analogs will depend on the long-term outcome of clinical studies.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Chlorambucil; Cyclophosphamide; Doxorubicin; Humans; Lymphoma, B-Cell; Palliative Care; Prednimustine; Prednisone; Prognosis; Retrospective Studies; Risk Assessment; Survival Rate; Vincristine
PubMed: 9178841
DOI: No ID Found -
Journal of Clinical Oncology : Official... Mar 1997To evaluate prospectively in patients with follicular lymphoma and a low tumor burden three therapeutic options: delay of any treatment until clinically meaningful... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Comparison in low-tumor-burden follicular lymphomas between an initial no-treatment policy, prednimustine, or interferon alfa: a randomized study from the Groupe d'Etude des Lymphomes Folliculaires. Groupe d'Etude des Lymphomes de l'Adulte.
PURPOSE
To evaluate prospectively in patients with follicular lymphoma and a low tumor burden three therapeutic options: delay of any treatment until clinically meaningful progression, immediate treatment with an oral alkylating agent, or treatment with a biologic response modifier, interferon alfa-2b.
PATIENTS AND METHODS
Newly diagnosed follicular lymphoma patients with a low tumor burden (n = 193) were randomly assigned to one of three arms: arm 1, no initial treatment (n = 66); arm 2, prednimustine 200 mg/m2/d for 5 days per month for 18 months (n = 64); or arm 3, interferon alfa 5 MU/d for 3 months then 5 MU three times per week for 15 months (n = 63). Clinical characteristics were similar in the three arms.
RESULTS
Overall response rates with prednimustine and interferon alfa were 78% and 70%, respectively. The overall response to therapy, when deferred, was similar at 70%. With a median follow-up duration of 45 months after randomization, the median freedom-from-treatment (FFT) interval was 24 months in arm 1 and the interval of freedom from treatment failure (FFTF) was 40 months in arm 2 and 35 months in arm 3. The median overall survival time was not reached and the overall survival rate at 5 years was 78% in arm 1, 70% in arm 2, and 84% in arm 3. Therefore, deferred treatment does not adversely influence survival at 5 years. Patients who progressed within 1 year had a significantly shorter survival duration (median, 48 months).
CONCLUSION
Delayed treatment is feasible in patients with follicular lymphoma and a low tumor burden. For patients with early progression, more intensive therapy should be considered. For others, because delay of treatment until significant clinical progression does not seem to hamper the prognosis or subsequent response to treatment, the long-term toxicity of alkylating agents can be reduced.
Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Disease Progression; Drug Administration Schedule; Female; Humans; Interferon-alpha; Lymphoma, Follicular; Male; Middle Aged; Prednimustine; Prospective Studies
PubMed: 9060552
DOI: 10.1200/JCO.1997.15.3.1110 -
European Journal of Cancer (Oxford,... Feb 1997The aim of this study was to assess the efficacy and toxicity of an idarubicin-prednimustine combination in advanced breast cancer. 19 patients received idarubicin 35... (Clinical Trial)
Clinical Trial
The aim of this study was to assess the efficacy and toxicity of an idarubicin-prednimustine combination in advanced breast cancer. 19 patients received idarubicin 35 mg/m2 day 1 and prednimustine 100 mg/m2 days 2-6, every 21 days. Three objective responses with a median duration of 7 months were observed. Tolerance was good. A further 23 patients were given idarubicin administered at 15 mg/m2 days 1, 2 and 3 and prednimustine at the aforementioned dosage. 8 (35%) showed an objective response (4 CRs, 4 PRs) with a median duration of 6 months. No severe toxicity was observed. Results suggest activity of idarubicin-prednimustine combinations in advanced breast cancer, and further studies are indicated since this regimen is easily administered, especially to elderly patients.
Topics: Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Drug Administration Schedule; Female; Humans; Idarubicin; Middle Aged; Prednimustine; Treatment Outcome
PubMed: 9135508
DOI: 10.1016/s0959-8049(96)00372-3 -
Journal of the National Cancer Institute Jan 1997
Topics: Aged; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Female; Hodgkin Disease; Humans; Mitochondria; Myoclonus; Phosphorylation; Prednimustine
PubMed: 8998190
DOI: 10.1093/jnci/89.2.173