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Annals of Oncology : Official Journal... Oct 2002The aim of this study was to analyze outcome of patients with Hodgkin's disease (HD) in whom first-line chemotherapy with mustine/vincristine/procarbazine/prednisone...
BACKGROUND
The aim of this study was to analyze outcome of patients with Hodgkin's disease (HD) in whom first-line chemotherapy with mustine/vincristine/procarbazine/prednisone (MOPP) had failed.
PATIENTS AND METHODS
From January 1982 to December 1989 among 210 patients treated with MOPP and radiotherapy to initial bulky sites, 65 patients were primary refractory to or relapsed after initial treatment.
RESULTS
Twenty-nine of 65 patients (44%) were primary refractory to initial chemotherapy, 20 relapsed within 12 months after complete remission (CR) and 16 relapsed after CR that lasted more than 12 months. Patients with primary refractory HD and early relapse (<12 months after CR) were treated with doxorubicin/bleomycin/vinblastine/darcarbazine. In patients with late relapse (>12 months after CR) MOPP was repeated. The median follow-up for all patients was 115 months. The overall response rate was 63%. Thirty-three patients (51%) achieved a second CR and eight patients (12%) partial response. Remission rate was greatest in patients with late relapse (CR >12 months) (75 versus 55% for early relapse versus 35% for primary refractory HD) (P <0.01). At 10 years, overall and failure-free survival rates were 21 and 16%, respectively. Patients who were in first remission longer than 12 months had a superior overall survival (37 versus 18% for early relapse) and failure-free survival (24 versus 10% for early relapse). No patient with primary refractory HD was alive beyond 52 months after initial treatment failure (P <0.01). Main prognostic factors were duration of the first remission and tumor bulk at relapse.
CONCLUSIONS
Our results confirm previous observations that a significant proportion of patients with HD who experience induction treatment failure cannot be cured with conventional treatment and probably need more aggressive therapy.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Croatia; Dacarbazine; Disease-Free Survival; Doxorubicin; Drug Resistance, Neoplasm; Female; Hodgkin Disease; Humans; Male; Mechlorethamine; Middle Aged; Prednisone; Procarbazine; Prognosis; Retrospective Studies; Salvage Therapy; Vinblastine; Vincristine
PubMed: 12377656
DOI: 10.1093/annonc/mdf271 -
Blood Mar 2003Although numerous reports indicate that patients receiving autotransplants for lymphoma are at increased risk for myelodysplastic syndrome (MDS)/acute myeloid leukemia...
Although numerous reports indicate that patients receiving autotransplants for lymphoma are at increased risk for myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), the separate contributions of pretransplantation- and transplantation-related therapy are not well characterized. We conducted a case-control study of 56 patients with MDS/AML and 168 matched controls within a cohort of 2 739 patients receiving autotransplants for Hodgkin disease or non-Hodgkin lymphoma at 12 institutions (1989-1995). Detailed abstraction of medical records was undertaken to determine all pre- and posttransplantation therapy, and transplantation-related procedures. In multivariate analyses, risks of MDS/AML significantly increased with the intensity of pretransplantation chemotherapy with mechlorethamine (relative risks [RRs] = 2.0 and 4.3 for cumulative doses < 50 mg/m2 and > or = 50 mg/m,2 respectively; trend over dose categories, P =.04) or chlorambucil (RRs = 3.8 and 8.4 for duration < 10 months or > or = 10 months, respectively; trend, P =.009), compared with cyclophosphamide-based therapy. Transplantation-conditioning regimens including total-body irradiation (TBI) at doses 12 Gy or less did not appear to elevate leukemia risk (RR = 1.3; P =.48) compared with non-TBI regimens; however, a statistically significant increased risk was found for TBI doses of 13.2 Gy (RR = 4.6; P =.03). Peripheral blood stem cells were associated with a nonsignificant increased risk of MDS/AML (RR = 1.8; P =.12) compared with bone marrow grafts. Our data show that type and intensity of pretransplantation chemotherapy with alkylating agents are important risk factors of MDS/AML following autotransplantation. Transplantation-related factors may also modulate this risk; however, the apparent contribution of high-dose TBI requires confirmation.
Topics: Acute Disease; Adolescent; Adult; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Case-Control Studies; Child; Chlorambucil; Cohort Studies; Cyclophosphamide; Dose-Response Relationship, Radiation; Female; Humans; Leukemia, Myeloid; Leukemia, Radiation-Induced; Lymphoma; Male; Mechlorethamine; Middle Aged; Multivariate Analysis; Myelodysplastic Syndromes; Neoplasms, Second Primary; Peripheral Blood Stem Cell Transplantation; Prednisone; Procarbazine; Risk; Transplantation Conditioning; Transplantation, Autologous; Vincristine; Whole-Body Irradiation
PubMed: 12393427
DOI: 10.1182/blood-2002-04-1261 -
Annals of Oncology : Official Journal... Nov 1994This study evaluated the therapeutic effect of the weekly administration of vinorelbine (5'-nor-anhydrovinblastine), a semisynthetic vinca alkaloid, in heavily... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
This study evaluated the therapeutic effect of the weekly administration of vinorelbine (5'-nor-anhydrovinblastine), a semisynthetic vinca alkaloid, in heavily pretreated patients with Hodgkin's disease.
PATIENTS AND METHODS
Twenty-four patients with Hodgkin's disease refractory or resistant to at least two chemotherapy regimens were enrolled in this study. Vinorelbine was administered in a weekly dose of 30 mg/m2 i.v. bolus and patients were evaluated after four courses. All but two were considered evaluable for drug response. The reasons for their exclusion were early death due to pancytopenia and loss to follow-up after two courses. In complete responders, six additional courses were administered; in all other patients, treatment was continued until their diseases progressed. Toxicity was evaluated in 23 patients according to the Common Toxicity Criteria.
RESULTS
Eleven of 22 evaluable patients (50%) showed objective response (complete 14% and partial 36%). The median duration of response was six months for both complete and partial responders (range 2-10 months). Thirteen patients are still alive and five are still on therapy. Grade 3-4 granulocytopenia was documented in 53% of patients and grade 3 infections in 13%. Anemia and thrombocytopenia were negligible. Nausea and vomiting were not observed; grade 2 alopecia occurred in only one patient. There were grade 3 reactions at the injection site in the first five patients, so a venous central access was utilized in the subsequent patients. Two patients had grade 1 constipation and only one developed an adynamic ileum. Although all patients had previously been treated with vinca alkaloid analogs, peripheral neuropathy was mild.
CONCLUSIONS
Our data indicate that vinorelbine is active as a single agent in heavily pretreated patients with Hodgkin's disease. The efficacy in patients pretreated with at least two vinca alkaloids suggests a possible absence of cross-resistance between vinorelbine and other vinka analogs. Toxicity is mild and reversible. The inclusion of vinorelbine in secondline combination chemotherapy regimens for Hodgkin's disease is strongly recommended.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Dacarbazine; Doxorubicin; Female; Follow-Up Studies; Hodgkin Disease; Humans; Male; Mechlorethamine; Prednisone; Procarbazine; Radiotherapy; Remission Induction; Salvage Therapy; Survival Rate; Vinblastine; Vincristine; Vinorelbine
PubMed: 7531487
DOI: 10.1093/oxfordjournals.annonc.a059010 -
British Journal of Cancer Jul 2017Hodgkin lymphoma (HL) survivors are at increased risk of second malignancies, but few studies have assessed colorectal cancer (CRC) risk after HL treatment. We assessed...
BACKGROUND
Hodgkin lymphoma (HL) survivors are at increased risk of second malignancies, but few studies have assessed colorectal cancer (CRC) risk after HL treatment. We assessed long-term, subsite-specific CRC risk associated with specific radiation fields and chemotherapy regimens.
METHODS
In a Dutch cohort of 3121 5-year HL survivors treated between 1965 and 1995, subsite-specific CRC incidence was compared with general population rates. Treatment effects were quantified by Cox regression analyses.
RESULTS
After a median follow-up of 22.9 years, 55 patients developed CRC. The standardized incidence ratios (SIR) was 2.4-fold increased (95% confidence interval (95%CI) 1.8-3.2), leading to 5.7 excess cases per 10 000 patient-years. Risk was still increased 30 years after HL treatment (SIR: 2.8; 95%CI: 1.6-4.6). The highest (SIR: 6.5, 95%CI: 3.3-11.3) was seen for transverse colon cancer (15.0 (95%CI: 4.3-40.8) after inverted-Y irradiation). A prescribed cumulative procarbazine dose >4.2 g m was associated with a 3.3-fold higher CRC risk (95%CI: 1.8-6.1) compared to treatment without procarbazine. Patients receiving >4.2 g m procarbazine and infradiaphragmatic radiotherapy had a hazard ratio of 6.8 (95%CI: 3.0-15.6) compared with patients receiving neither treatment, which is significantly higher than an additive joint effect (P=0.004).
CONCLUSIONS
Colorectal cancer surveillance should be considered for HL survivors who received Infradiaphragmatic radiotherapy and a high cumulative procarbazine dose.
Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Colon; Colorectal Neoplasms; Diaphragm; Doxorubicin; Female; Follow-Up Studies; Hodgkin Disease; Humans; Male; Mechlorethamine; Middle Aged; Neoplasms, Radiation-Induced; Neoplasms, Second Primary; Netherlands; Prednisone; Procarbazine; Rectum; Risk Factors; Survivors; Vinblastine; Vincristine; Young Adult
PubMed: 28632726
DOI: 10.1038/bjc.2017.177 -
Blood Jun 2006From 1989 to 1996, 533 eligible patients with stage IIIB/IV Hodgkin lymphoma (HL) were randomly assigned to receive 6 cycles of hybrid MOPP/ABV (mechlorethamine,... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Long-term results and competing risk analysis of the H89 trial in patients with advanced-stage Hodgkin lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte (GELA).
From 1989 to 1996, 533 eligible patients with stage IIIB/IV Hodgkin lymphoma (HL) were randomly assigned to receive 6 cycles of hybrid MOPP/ABV (mechlorethamine, vincristine, procarbazine, prednisone/Adriamycin [doxorubicin], bleomycin, vinblastine; n = 266) or ABVPP (doxorubicin, bleomycin, vinblastine, procarbazine, prednisone; n = 267). Patients in complete remission (CR) or partial response of at least 75% after 6 cycles received 2 cycles of consolidation chemotherapy (CT) (n = 208) or subtotal nodal irradiation (RT) (n = 210). A better survival probability was observed after ABVPP alone: the 10-year overall survival (OS) estimates were 90% for ABVPP x 8, 78% for MOPP/ABV x 8, 82% for MOPP/ABV with RT, and 77% for ABVPP x 6 with RT (P = .03); and the 10-year disease-free survival (DFS) estimates were 70%, 76%, 79%, and 76%, respectively (P = .09). The 10-year DFS estimates for patients treated with consolidation CT or RT were 73% and 78% (P = .07), and OS estimates were 84% and 79%, respectively (P = .29). These results showed that RT was not superior to consolidation CT after a doxorubicin-induced CR in patients with advanced HL. An analysis of competing risks identified age more than 45 years as a significant risk factor for death, relapse, and second cancers. Prospective evaluation of late adverse events may improve the management of patients with HL.
Topics: Adolescent; Adult; Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Disease-Free Survival; Doxorubicin; Evaluation Studies as Topic; Female; Hodgkin Disease; Humans; Longitudinal Studies; Lymphatic Irradiation; Male; Mechlorethamine; Middle Aged; Neoplasm Staging; Neoplasms, Second Primary; Prednisolone; Prednisone; Procarbazine; Recurrence; Retrospective Studies; Risk Factors; Vinblastine; Vincristine
PubMed: 16478882
DOI: 10.1182/blood-2005-11-4429 -
Annals of Oncology : Official Journal... Sep 1993Patients with Hodgkin's disease whose initial complete remissions (CR) after primary chemotherapy were longer than 1 year are thought to have better prognoses than...
BACKGROUND
Patients with Hodgkin's disease whose initial complete remissions (CR) after primary chemotherapy were longer than 1 year are thought to have better prognoses than patients whose initial remissions were shorter than 1 year. However, only a few studies have analyzed the long-term survival in addition to the results of retreatment in patients relapsing after CR lasting more than 1 year.
PATIENTS AND METHODS
We analyzed the data of 40 patients with Hodgkin's disease who were treated in a single institution and whose CR were > 1 year after primary chemotherapy. Therapy at relapse was not standardized: of 36 patients evaluable for response, 29 received second-line chemotherapy and 7 received radiotherapy alone.
RESULTS
Sixty-five percent of the patients obtained CR (median duration: 21 months). Sixty-eight percent of the complete responders relapsed again; however, long-lasting third and fourth remissions were observed. All of the 7 patients whose retreatment consisted of radiotherapy alone obtained CR, but only 1 is in continuous CR. The presence of nodular sclerosing histologic subtype, the absence of extranodal involvement and the use of hybrid MOPP/ABVD or ABVD alone as salvage treatment are independently associated with a higher CR rate and a higher probability of 5-year survival. The 5-year survival for all 40 patients is 49%. For the patients obtaining CR, the 5-year survival and the 5-year relapse-free survival are 76% and 25%, respectively. However, the survival curve continues to fall in the succeeding years because of third and fourth relapses and the occurrence of secondary acute leukemia and non-Hodgkin's lymphoma.
CONCLUSIONS
A high percentage of patients relapsing more than 12 months after primary chemotherapy can obtain second CR. Even if most of our patients eventually relapse, third and fourth CRs are not uncommon. However, the long-term survival is low and it is further diminished by secondary leukemia and non-Hodgkin's lymphoma.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Dacarbazine; Doxorubicin; Female; Hodgkin Disease; Humans; Male; Mechlorethamine; Middle Aged; Prednisone; Procarbazine; Prognosis; Recurrence; Remission Induction; Salvage Therapy; Survival Rate; Time Factors; Vinblastine; Vincristine
PubMed: 7694635
DOI: 10.1093/oxfordjournals.annonc.a058620 -
American Journal of Hematology Jul 1999We retrospectively analyzed 57 patients with advanced stage (stage III/IV) or unfavorable (presence of B symptoms or bulky disease) Hodgkin's disease from January 1977...
We retrospectively analyzed 57 patients with advanced stage (stage III/IV) or unfavorable (presence of B symptoms or bulky disease) Hodgkin's disease from January 1977 to December 1997. There were 29 male and 28 female patients. The median age was 27 years old (range, 13-59). Lactate dehydrogenase levels ranged from 104 units/l to 2320 units/l (median, 433). Eighteen (31.6%), 13 (22.8%), and 26 (45.6%) patients had stage II bulky, stage III, and stage IV disease, respectively. Twenty-five (44%) patients had B symptoms. One (1.8%), 3 (5.3%), 36 (63.2%), and 17 (29.8%) had lymphocyte predominant, lymphocyte depleted, nodular sclerosis, and mixed cellularity histology, respectively. Chemotherapy regimens included mechlorethamine, vincristine, procarbazine, prednisone (MOPP) (n = 9), adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) (n = 23), MOPP alternating with ABVD (n = 13), and COPP-ABV hybrid (n = 12). Complete remission was achieved in 47 (82.4%) patients. Eleven patients (23%) relapsed after the first complete remission and four (36%) attained a second complete remission with salvage chemotherapy. Projected overall survival was 69.0% at 10 years and 20 years. Disease-free survival rates were 71% at 10 years and 20 years. Of the potential prognostic factors analyzed (age, sex, stage, lactate dehydrogenase, serum albumin level, regimen, B symptoms and bulky disease) by using the Cox regression model, only a low albumin level was found to adversely affect overall survival (P = 0.003). In conclusion, despite the relative low incidence of Hodgkin's disease in Hong Kong Chinese, the treatment outcomes in patients with advanced stage or unfavorable Hodgkin's disease is comparable to Caucasian patients.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Disease-Free Survival; Doxorubicin; Female; Hodgkin Disease; Hong Kong; Humans; Male; Mechlorethamine; Middle Aged; Neoplasm Staging; Prednisone; Procarbazine; Retrospective Studies; Survival Analysis; Time Factors; Vinblastine; Vincristine
PubMed: 10398307
DOI: 10.1002/(sici)1096-8652(199907)61:3<159::aid-ajh1>3.0.co;2-g -
British Journal of Cancer Apr 1991From 1979-1983, 299 patients with stage III or IV Hodgkin's disease (HD) were randomised to receive cyclical chemotherapy with MOPP (mustine, Oncovin, procarbazine,... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
British National Lymphoma Investigation randomised study of MOPP (mustine, Oncovin, procarbazine, prednisolone) against LOPP (Leukeran substituted for mustine) in advanced Hodgkin's disease--long term results.
From 1979-1983, 299 patients with stage III or IV Hodgkin's disease (HD) were randomised to receive cyclical chemotherapy with MOPP (mustine, Oncovin, procarbazine, prednisone) or LOPP (Leukeran substituted for mustine). Two hundred and ninety patients were evaluable. There was no statistically significant difference between the complete remission (CR) rates (63% for MOPP, 57% for LOPP), percentage of patients remaining disease free at 5 years (38% for MOPP, 35% for LOPP) and overall survival at 5 years (65% for MOPP, 64% for LOPP). On multivariate analysis younger age, grade I histopathology, absence of systemic symptoms, and normal albumin level were favourable prognostic factors for survival. Acute toxicity in the form of nausea/vomiting, myelosuppression, and phlebitis were less with LOPP than MOPP. Deaths in both groups were usually due to disseminated Hodgkin's disease; there were no infective deaths in the absence of Hodgkin's disease. Second malignancies occurred in six patients treated with MOPP--three acute myeloid leukaemia (AML), one non-Hodgkin's lymphoma (NHL), two carcinomas (Ca); with LOPP, four second malignancies occurred (one AML, one NHL, two Ca). These long term results confirm that LOPP is as effective as MOPP, and less toxic, in the treatment of advanced Hodgkin's disease.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Chlorambucil; Female; Follow-Up Studies; Hodgkin Disease; Humans; Male; Mechlorethamine; Middle Aged; Multivariate Analysis; Neoplasms; Prednisolone; Prednisone; Procarbazine; Prognosis; Remission Induction; Vincristine
PubMed: 2021542
DOI: 10.1038/bjc.1991.134 -
British Journal of Cancer 1997Risk of second primary malignancy was assessed in follow-up to June 1991 of 1039 patients first treated for Hodgkin's disease at the Royal Marsden Hospital during...
Risk of second primary malignancy was assessed in follow-up to June 1991 of 1039 patients first treated for Hodgkin's disease at the Royal Marsden Hospital during 1963-91. A total of 77 second malignancies occurred. There were significantly raised risks of stomach [standardized incidence ratio (SIR)=4.0], lung (SIR=3.8), bone (SIR=26.5), soft tissue (SIR=16.9) and non-melanoma skin (SIR=3.9) cancers, non-Hodgkin's lymphoma (SIR=4.6), and acute and non-lymphocytic leukaemia (SIR=31.3), with a relative risk of 3.3 for all second cancers other than non-melanoma skin cancer. Solid cancer risk was raised to a similar extent in patients treated only with radiotherapy (SIR=2.6, P<0.001), only with chemotherapy (SIR=2.1, P=0.08) and with both (SIR=3.1, P<0.001). Leukaemia risk was raised only in those receiving chemotherapy, whether alone or with radiotherapy. The relative risk for solid cancers was much greater in patients who were younger at first treatment (trend P<0.001), whereas leukaemia risk was greatest for those first treated at ages 25-44. For solid cancers (P<0.001) but not leukaemia (P=0.05) there was a strong gradient of greater relative risks at younger attained ages. The relative risk of second cancers overall was 27.5 at ages under 25 and 2.0 at ages 55 and above. Leukaemia and solid cancer risks in patients treated with chlorambucil, vinblastine, procarbazine and prednisone (ChlVPP) were not significantly greater than those in patients treated with mustine, vincristine, procarbazine and prednisone (MOPP). Number of cycles of chemotherapy was significantly related to risk of leukaemia (P<0.001), and there was a trend in the same direction for solid cancers (P=0.07). The study adds to evidence that alkylating chemotherapy may increase the risk of solid cancers, and that ChlVPP does not provide a less carcinogenic alternative to MOPP chemotherapy. The very large relative risks found for solid cancers at young attained ages and in patients treated when young may have important implications as, in the long term, the majority of second malignancies after Hodgkin's disease are solid cancers. The risks of solid malignancies need clarification by larger collaborative epidemiological studies.
Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Chlorambucil; Female; Hodgkin Disease; Humans; Male; Mechlorethamine; Middle Aged; Neoplasms, Second Primary; Prednisone; Procarbazine; Risk; Risk Factors; Vinblastine; Vincristine
PubMed: 9000608
DOI: 10.1038/bjc.1997.19 -
British Journal of Haematology Jul 2002Between 1972 and 1988, 869 adult patients received MOPP (mechlorethamine, vincristine, procarbazine and prednisone; 462 patients) or ABVD (doxorubicin, bleomycin,... (Comparative Study)
Comparative Study
Between 1972 and 1988, 869 adult patients received MOPP (mechlorethamine, vincristine, procarbazine and prednisone; 462 patients) or ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine; 373 patients) and subsequent high-dose irradiation for Hodgkin's disease. Nine patients developed a leukaemia after MOPP and four after ABVD; 11 patients were diagnosed as acute non-lymphoblastic leukaemia (ANLL) and two as acute lymphoblastic leukaemia (ALL). Both cases of ALL were observed after ABVD and were associated with a 11q23 translocation. The 15-year actuarial risk of secondary leukaemia was 2.4% for the whole group of patients, 3.4% after MOPP and 1.3% after ABVD. For the MOPP subgroup, the risk of leukaemia was significantly associated with the extent of irradiation: 2.4% for limited irradiation and 13.9% for extended irradiation (P < 0.001). For the ABVD subgroup, this risk remained low (1.3%) whatever the type of irradiation. Concerning ANLL, the MOPP regimen was significantly associated with a higher risk: 3.4% versus 0.7% for ABVD (P
MOPP. However, a low risk of ALL with a 11q23 translocation related to topoisomerase II inhibitors was observed. Topics: Actuarial Analysis; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Dacarbazine; Doxorubicin; Female; Follow-Up Studies; Hodgkin Disease; Humans; Leukemia; Leukemia, Myeloid, Acute; Male; Mechlorethamine; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Procarbazine; Prospective Studies; Radiotherapy Dosage; Radiotherapy, Adjuvant; Risk; Vinblastine; Vincristine
PubMed: 12100147
DOI: 10.1046/j.1365-2141.2002.03564.x