Low-dose radiation therapy and reduced chemotherapy in childhood Hodgkin's disease: the experience of the French Society of Pediatric Oncology.

PURPOSE: With the aim of decreasing undesirable side effects of therapy, we investigated the reduction of both chemotherapy and radiation therapy (RT) in children with Hodgkin's disease, and compared Adriamycin (doxorubicin; Farmitalia Carlo Erba, Rueil-Malmaison, France), bleomycin, vinblastine, and dacarbazine (ABVD) alone to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and ABVD in favorable cases and assessed the effectiveness of low-dose RT (20 Gy) after good response to chemotherapy. PATIENTS AND METHODS: A French national study began in 1982 that included 238 pediatric patients with Hodgkin's disease. Initial staging was clinical and without laparotomy. In patients with localized disease (IA-IIA), an equivalence trial compared the effectiveness of four cycles of ABVD with two cycles of ABVD that were alternated with two cycles of MOPP. Patients with more advanced disease (IB-IIB-III-IV) received three courses of MOPP that was alternated with three courses of ABVD. All of the patients who achieved a good remission after chemotherapy were administered 20 Gy RT, which was limited to the initially involved areas for localized disease, and encompassed the paraaortic nodes and the spleen as well for more advanced stages. When a good remission was not obtained, 40 Gy RT was administered. RESULTS: At the completion of chemotherapy, 227 patients (97%) were considered good responders, whereas 11 did not achieve a good remission. With a median follow-up of 6 years, the 6-year actuarial survival was 92% and the disease-free survival was 86%. The relapse-free survival in favorable stages was 90% in the ABVD arm and was 87% in the MOPP and ABVD arm. In June 1987, inclusion of stage IV patients was discontinued because of poor results. CONCLUSIONS: Present findings indicate that (1) in favorable stages, ABVD alone and alternating MOPP and ABVD are equivalent, and (2) chemotherapy followed by 20 Gy RT represents a valid therapeutic approach in the vast majority of children with Hodgkin's disease.     

Initial chemotherapy and low-dose radiation in limited fields in childhood Hodgkin's disease: results of a joint cooperative study by the French Society of Pediatric Oncology (SFOP) and H?pital Saint-Louis, Paris

To minimize the drawbacks of treatment we had shown in a previous study that it was possible after chemotherapy to limit the radiation fields to the involved areas only. Pursuing our policy of deescalation, we started in January 1982 a study in 29 French pediatric and hematologic centers, with two aims: (1) To compare the efficacy of 4 cycles of two different chemotherapeutic regimens (4 ABVD vs 2 MOPP + ABVD) in early stages (CSIA and II A) while other stages would receive 6 cycles of the same regimen (3 MOPP + 3 ABVD); (2) To evaluate the efficacy of irradiation given at a low dose (20 Gy) in the patients who had a minimum 70% reduction of the size of their nodes (good responders). From January 1982 to March 1987, 174 patients were entered in this study, of whom 157 completed their treatment program at the time of analysis. On completion of chemotherapy, 94% were considered as good responders and were irradiated to 20 Gy. Only 6 patients received a mediastinal boost (up to 40 Gy). Of the 6% (10/157) poor responders a complete remission was obtained in 6 after 40 Gy. Among the good responders, 5 patients relapsed, with only 3 within an area irradiated to 20 Gy. So that 4 nodal relapses occurred among 364 involved lymph areas. The actuarial survival at 42 months (median 30 months) is 95% (IA + IIA = 100%, IB + IIB + III = 94% and IV = 80%) and the disease-free survival 88% (respectively 94, 93 and 54). Until now there is no statistically significant difference between the 2 randomized arms. This study shows that it is possible to achieve a durable remission in most children treated with a less toxic protocol eliminating or reducing Nitrogen Mustard and reducing the dose of irradiation. Less late complications and sequelae are expected with a longer follow-up.     

Combination chemotherapy of Hodgkin's disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide versus MOPP.

This paper reports the preliminary results of a controlled study randomizing MOPP vs. a new four-drug combination (ABVD) in advanced Hodgkin's disease. ABVD consists of 6 cycles of adriamycin, bleomycin, vinblastine, and imidazole carboxamide. The purpose for designing this new combination was two-fold: to compare the efficacy of ABVD with MOPP, and to demonstrate absence of cross-resistance between the two regimens. Of 60 patients entered into the study, 45 (MOPP25, ABVD20) are presently evaluable for the analysis of remission induction. No patient was previously treated with chemotherapy; 20% had relapsed after primary radiotherapy. Whenever possible, complete remission was defined also through rebiopsy of known organ involvement. Complete remission occurred in 76% of patients treated with MOPP and in 75% of those given ABVD, with no difference between the two regimens as far as stage (IIIB-IIIS and IV), histologic type, and prior irradiation were concerned. Crossover carried out for progressive disease or for relapse after initial remission showed absence of cross-resistance between MOPP and ABVD. Toxic manifestations after ABVD were in general well tolerated and reversible. The percent of optimal dose for each drug was as follows: adriamycin 87%, vinblastine 87%, bleomycin 96%, and imidazole carboxamide 96%. These preliminary results indicate that in terms of complete remission, ABVD could represent a successful alternative to MOPP to be used either in MOPP failures or in sequential combination with MOPP. However, the lack of long-term followup limits at the present time an adequate comparison between the two treatments.     

Testicular disease in childhood B-cell non-Hodgkin's lymphoma: the French Society of Pediatric Oncology experience.

PURPOSE: To investigate whether testicular disease in childhood B-cell lymphoma should continue to be considered a sanctuary site, as it is with other lymphoid malignancies such as acute lymphoblastic leukemia. PATIENTS AND METHODS: Seven hundred forty-two children with B-cell non-Hodgkin's lymphoma were included in the LMB protocols of the French Society of Pediatric Oncology from February 1981 to May 1994. Thirty patients (5.3%) had testicular involvement at diagnosis. We describe the clinical presentation and outcome of these 30 patients, who were treated without local radiation therapy. RESULTS: Five patients underwent diagnostic orchidectomy. The median patient age was 8.5 years (range, 2 to 14 years), and their cancers were stage III (18 patients), stage IV (five patients), and B-cell acute lymphoblastic leukemia (seven patients). Five patients had central nervous system involvement. Twenty-eight patients (95%) achieved complete remission. Twenty-six patients are alive without progressive disease (median follow-up, 6.5 years). CONCLUSION: Testicular disease does not seem to confer a poor prognosis, and it is curable with intensive combination chemotherapy alone. Local treatment (surgery or radiation) is avoidable; therefore, gonadal function can be preserved.     

Treatment of unfavorable childhood Hodgkin's disease with VEPA and low-dose, involved-field radiation.

PURPOSE: Between January 1990 and April 1993, 56 pediatric patients with Hodgkin's disease were treated on a single-arm trial at three institutions with a regimen designed to maintain high cure rates while minimizing the potential late effects of treatment, such as infertility, second malignant neoplasms, and cardiopulmonary injury. PATIENTS AND METHODS: The regimen used combined-modality therapy with six cycles of vinblastine, etoposide, prednisone, and doxorubicin (VEPA) chemotherapy and low-dose, involved-field radiation. Unfavorable features comprised bulky presentations of localized (stage I or II) disease or advanced (stage III or IV) Hodgkin's disease. RESULTS: Of 56 patients enrolled, 26 (46%) had unfavorable presentations of stage I/II disease and 30 (54%) had advanced (stage III/IV) disease. Seventy-nine percent of the patients are alive without disease at a median follow-up time of 8.9 years from diagnosis. Nineteen patients had events at a median of 1.5 years (range, 0.4 to 7.9 years) from diagnosis; 17 patients relapsed, one died of cardiomyopathy, and one died of accidental injuries. Survival and event-free survival (EFS) estimates at 5 years for the entire cohort were 81.9% (SE, 5.2%) and 67.8% (SE, 6.3%), respectively. Five-year EFS by stage was 100% for stage I, 79.2% (SE, 8.3%) for stage II, 70% (SE, 14.5%) for stage III, and 49.5% (SE, 11.3%) for stage IV patients. CONCLUSION: Combined-modality therapy with VEPA chemotherapy and low-dose, involved-field radiation is adequate for disease control of early-stage patients with unfavorable features, but it is inferior to other standard regimens for advanced-stage patients.     

The combination of epirubicin, bleomycin, vinblastine and prednisone (EBVP) before radiotherapy in localized stages of Hodgkin's disease. Phase II trials

A new regimen of chemotherapy was used to reduce toxicity of ABVD: adriamycin is replaced by epirubicin and dacarbazine by prednisone. Thirty eight patients with Hodgkin's disease, stage I to IIIA, previously untreated, received three courses of this regimen before radical radiotherapy. Gastro-intestinal toxicity and alopecia appeared less marked than with ABVD. Immediate efficacy is similar with 80% of complete remission (one third observed at day 28) and only 2 failures. This regimen appears thus as a clear improvement in the treatment of patients with Hodgkin's disease and deserves larger comparison with previously used chemotherapy in a more extensive controlled trial.     

Combination chemotherapy of MOPP-resistant Hodgkin's disease with adriamycin, bleomycin, dacarbazine and vinblastine (ABDV).

Twenty-four patients with advanced Hodgkin's disease, resistant to the MOPP regimen, were treated with a combination of Adriamycin, bleomycin, dacarbazine and vinblastine (ABDV). Fifteen (63%) achieved objective remission, 14 partial remissions and one complete remission. The median duration of remission in this group of patients was 6.5 months; four of the 15 patients are still in remission (8+, 8+, 9+, 10+ months). Objective remission occurred rapidly within 1.5 months. Regression was evident in disease within nodes, lung, liver and bone. Toxic manifestations caused by ABDV were well tolerated and reversible. In one patient death was directly attributed to drug toxicity. This combination has produced a better rate and duration of remission than that reported with single agent chemotherapy in MOPP-resistant patients with Hodgkin's disease. In our hands, ABDV did not equal the recent results reported with Bleomycin-CCNU-Velban in a seemingly similar group of patients.     

Standard-risk medulloblastoma treated by adjuvant chemotherapy followed by reduced-dose craniospinal radiation therapy: a French Society of Pediatric Oncology Study.

OBJECTIVE: The primary objective of this study was to decrease the late effects of prophylactic radiation without reducing survival in standard-risk childhood medulloblastoma. PATIENTS AND METHODS: Inclusion criteria were as follows: children between the ages of 3 and 18 years with total or subtotal tumor resection, no metastasis, and negative postoperative lumbar puncture CSF cytology. Two courses of eight drugs in 1 day followed by two courses of etoposide plus carboplatin (500 and 800 mg/m(2) per course, respectively) were administered after surgery. Radiation therapy had to begin 90 days after surgery. Delivered doses were 55 Gy to the posterior fossa and 25 Gy to the brain and spinal canal. RESULTS: Between November 1991 and June 1998, 136 patients (median age, 8 years; median follow-up, 6.5 years) were included. The overall survival rate and 5-year recurrence-free survival rate were 73.8% +/- 7.6% and 64.8% +/- 8.1%, respectively. Radiologic review showed that 4% of patients were wrongly included. Review of radiotherapy technical files demonstrated a correlation between the presence of a major protocol deviation and treatment failure. The 5-year recurrence-free survival rate of patients included in this study with all optimal quality controls of histology, radiology, and radiotherapy was 71.8% +/- 10.5%. In terms of sequelae, 31% of patients required growth hormone replacement therapy and 25% required special schooling. CONCLUSION: Reduced-dose craniospinal radiation therapy can be proposed in standard-risk medulloblastoma provided staging and radiation therapy are performed under optimal conditions.     

Successful treatment of metastatic thymic carcinoma with cisplatin, vinblastine, bleomycin, and etoposide chemotherapy.

Thymic carcinomas are rare malignant neoplasms of the thymic epithelium that are distinguished from the malignant thymomas by the presence of cytologic atypia. Thymic carcinomas may metastasize outside of the thorax and are associated with a very poor prognosis. Complete responses of thymic carcinoma to chemotherapy alone have not been reported. A 21-year-old man with metastatic undifferentiated carcinoma of probable thymic origin is presented who achieved a pathologic complete response with cisplatin, vinblastine, and bleomycin chemotherapy. Additional consolidative chemotherapy with cisplatin and etoposide was administered. The patient remains disease-free 5 years after diagnosis. Cisplatin, vinblastine, and bleomycin chemotherapy appears to have significant activity against thymic carcinoma.     

Hodgkin's disease in 35 patients with HIV infection: An experience with epirubicin, bleomycin, vinblastine and prednisone chemotherapy in combination with antiretroviral therapy and primary use of G-CSF

Background: The optimal therapeutic approach for patients with Hodgkin's disease and human immunodeficiency virus infection (HD–HIV) is unknown. In an attempt to improve the results previously obtained with EBV (epirubicin, bleomycin and vinblastine) without G-CSF (Cancer 1994; 73: 437–44), in January 1993 we started a trial using chemotherapy (CT) consisting of EBV plus prednisone (EBVP), concomitant antiretroviral therapy (zidovudine, AZT or dideoxinosyne, DDI) , and G-CSF.Patients and methods: Up to August, 1997, 35 (30 M/5 F) consecutive previously untreated patients (median age 34, range 21–53 years) with HD–HIV were enrolled in the European Intergroup Study HD–HIV. Their median performance status was 1 (range 1–3). At diagnosis of HD, 26% of the patients had AIDS, 90% had B symptoms at HD presentation and 83% had advanced-stage HD. Patients received E 70 mg/m2 i.v. on day 1, B 10 mg/m2 i.v. on day 1, V 6 mg/m2 i.v. on day 1 and P 40 mg/m2 p.o. from day 1 to day 5 (EBVP). Courses were repeated every 21 days for six cycles. AZT (250 mg × 2/day), or DDI (200 or 300 mg × 2/day) if AZT had been previously used, were given orally from the beginning of CT. G-CSF was given at the dose of 5 mcg/kg/day s.c. from day 6 to day 20 in all cycles.Results: An overall response rate of 91% was observed. There were 74% complete responses (CR) and 17% partial responses (PR). Toxicity was moderate, with grade 3–4 leukopenia and thrombocytopenia in 10 (32%) and three (10%) patients, respectively. The median number of administered cycles was 6 (range 3–6). Twenty-three of 35 patients received AZT and nine patients received DDI. Three (8%) patients had opportunistic infections (OI) during or immediately after CT. The median CD4+ cell count was 219/mm3 (6–812) at HD diagnosis and 220/mm3 (2–619) after the end of combined therapy, and these numbers remained unchanged. Ten of 26 (38%) patients who achieved CR relapsed. Twenty-three patients died of HD progression alone or in association with OI, being the cause of death in 48% and 9% of patients respectively. The median survival was 16 months, with a survival rate of 32% and a disease-free survival of 53% at 36 months.Conclusions: The combined antineoplastic and antiretroviral treatment is feasible, but HD in HIV setting is associated with a more adverse prognosis than in the general population. Although the CR rate obtained was satisfactory, the relapse rate was high. Furthermore, comparison of the results of our two consecutive prospective studies demonstrated no overall improvement in the current trial with respect to the CR rate and survival.     

Recovery of sperm production following radiation therapy for Hodgkin's disease after induction chemotherapy with mitoxantrone, vincristine, vinblastine, and prednisone (NOVP)

PURPOSE: The effect on human male fertility of radiotherapy following chemotherapy for the treatment of Hodgkin's disease (HD) is unknown. The impact of radiation therapy, given after mitoxantrone, vincristine, vinblastine, and prednisone (NOVP) chemotherapy, on sperm production is the focus of this study. PATIENTS: Serial semen analyses were performed on 34 patients with HD Stages I-III before NOVP chemotherapy, after chemotherapy prior to radiation, and after radiation therapy. The most inferior radiation portals for patients were: mantle, 1 patient; paraaortic-spleen, 3 patients; upper abdomen, 24 patients; abdominal spade, 4 patients; and pelvic, 2 patients. Testicular radiation dose measurements were available for 20 of these patients. RESULTS: Before the start of radiation, 90% of patients were normospermic. The magnitude of the decline in sperm counts was related to the measured testicular dose and/or radiation fields employed. The minimum postradiotherapy counts, expressed as a fraction of pretreatment counts, for the various treatment groups are as follows: paraaortic-spleen, 20%; upper abdomen, testicular dose < 30 cGy, 4%; upper abdomen, testicular dose 30-39 cGy, 0.9%; abdominal spade, 0.02%; and pelvis, 0%. The time to nadir of sperm counts averaged 4.5 months. Recovery to normospermic levels occurred in 96% of patients, with most recovering to that level within 18 months. CONCLUSION: The effect of radiation following NOVP chemotherapy on sperm counts was no greater than would be expected with radiation therapy alone. In most patients, sperm counts recovered to levels compatible with normal fertility.     

New combination of epirubicine, bleomycin, vinblastine and prednisone (EBVP II) before radiotherapy in localized stages of Hodgkin's disease. Phase II trial in 50 patients

A new regimen of chemotherapy was used to reduce toxicity of EBVP I: the number of injections and the doses of bleomycin and vinblastine were reduced by half, the duration of treatment by third. Fifty patients with Hodgkin's disease stage I to IIIA, previously untreated, received three courses of this regimen before radiotherapy. Gastro-intestinal toxicity was similar and alopecia was more marked than with EBVP I. Immediate efficacy is similar, with 90% of complete remission and only one failure. This regimen is shorter and more intensive than EBVP I. It deserves larger comparison with previously used chemotherapy in a more extensive controlled trial.     

Treatment of MOPP-refractory Hodgkin's disease with vinblastine, doxorubicin, bleomycin, CCNU, and dacarbazine

Eighteen patients with advanced Hodgkin's disease, refractory to combination chemotherapy with nitrogen mustard, vincristine, prednisone, and procarbazine (MOPP), were treated with vinblastine, doxorubicin (Adriamycin), bleomycin, CCNU, and dacarbazine (DTIC) (VABCD). Fifteen patients had Stage IV disease and 11 had systemic symptoms. Although hematologic toxicity was considerable, there was no drug related mortality. Eight patients achieved a complete remission (CR), and five are currently in a continuous CR of five, 24, 30, 34, and 36 months duration, respectively. An additional patient had a 30-month CR and relapsed with localized lymphadenopathy and is currently disease-free following involved-field radiotherapy 46 months from initiation of VABCD. This study suggests that long-term disease-free survival and potential cure can be achieved with VABCD in MOPP-refractory Hodgkin's disease.     

Consolidation radiation after complete remission in Hodgkin's disease following six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy: is there a need?

PURPOSE: Combined modality treatment using multidrug chemotherapy (CTh) and radiotherapy (RT) is currently considered the standard of care in early stage Hodgkin's disease. Its role in advanced stages, however, continues to be debated. This study was aimed at evaluating the role of consolidation radiation in patients achieving a complete remission after six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy using event-free survival (EFS) and overall survival (OS) as primary end points. PATIENTS AND METHODS: Two hundred and fifty-one patients with Hodgkin's disease attending the lymphoma clinic at the Tata Memorial Hospital (Mumbai, India) from 1993 to 1996 received induction chemotherapy with six cycles of ABVD after initial staging evaluation. A total of 179 of 251 patients (71%) achieved a complete remission after six cycles of ABVD chemotherapy and constituted the randomized population. Patients were randomly assigned to receive either consolidation radiation or no further therapy. RESULTS: With a median follow-up of 63 months, the 8-year EFS and OS in the CTh-alone arm were 76% and 89%, respectively, as compared with 88% and 100% in the CTh+RT arm (P =.01; P =.002). Addition of RT improved EFS and OS in patients with age < 15 years (P =.02; P =.04), B symptoms (P =.03; P =.006), advanced stage (P =.03; P =.006), and bulky disease (P =.04; P =.19). CONCLUSION: Our study suggests that the addition of consolidation radiation helps improve the EFS and OS in patients achieving a complete remission after six cycles of ABVD chemotherapy, particularly in the younger age group and in patients with B symptoms and bulky and advanced disease.     

Intensive chemotherapy and low-dose radiotherapy for the treatment of advanced-stage Hodgkin's disease in pediatric patients: a Pediatric Oncology Group study.

Sixty-two patients with advanced-stage Hodgkin's disease and a median age of 12 years (range, 3 to 22 years) were treated with four cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) alternating with four cycles of doxorubicin, vinblastine, bleomycin, and dacarbazine (ABVD) followed by low-dose radiotherapy (RT). We determined the feasibility, immediate safety, and rapidity of response of patients to this regimen, as well as the relationship between prognostic factors and the rate of complete remission (CR), event-free survival (EFS), and overall survival. Therapy was well tolerated, and the major toxicity was hematopoietic. At the end of chemotherapy, 54 of 62 patients (87%) were in CR by clinical restaging, with a biopsy of residual disease where necessary. The actuarial 3-year EFS is 77% (SE, 11%), with a median follow-up of 35 months, and the survival is 91% (SE, 7%). With respect to EFS, female patients and those with stage II or III disease fared statistically better than males and patients with stage IV disease, respectively. Six patients have died: three of progressive Hodgkin's disease, one of secondary acute myelocytic leukemia (AML), one of secondary non-Hodgkin's lymphoma (NHL), and one of overwhelming bacterial sepsis. The Pediatric Oncology Group (POG) is currently engaged in a randomized study of these eight cycles of chemotherapy with and without RT to assess the role of RT in achieving comparable results.     

Treatment of MOPP-resistant Hodgkin's disease with adriamycin,bleomycin, vinblastine and dacarbazine (ABVD)

ABVD chemotherapy (adriamycin, bleomycin, vinblastine, dacarbazine) was given in monthly courses to 20 patients with Hodgkin's disease resistant to MOPP. Complete responses were achieved in 10 of the 18 evaluable patients (55%). Responses occurred rapidly with a median of 3 months. Nine of the 10 complete responders are presently off all therapy and remain disease-free after 9–60 months. The actuarial median survival for all patients is 38 months. Toxicity caused by ABVD was acceptable. ABVD is a useful salvage chemotherapy program for patients with Hodgkin's disease resistant to MOPP.     

Localized pelvic neuroblastoma: excellent survival and low morbidity with tailored therapy--the 10-year experience of the French Society of Pediatric Oncology.

PURPOSE: To assess the results and morbidity of treatment of children with localized pelvic neuroblastoma (NB). PATIENTS AND METHODS: All consecutive cases of localized pelvic NB registered in the French multicenter prospective studies NBL90 and NBL94 between 1990 and 1999 were reviewed. Resectability was decided on the basis of clinical and radiologic evaluation. In unresectable tumors, primary chemotherapy (combinations of carboplatin-etoposide and vincristine-cyclophosphamide-doxorubicine) was administered before surgery. RESULTS: Forty-seven children (with 26 resectable tumors and 21 unresectable) were included in this study. At the end of treatment, 31 children were in complete remission (66%). Long-term neurologic sequelae were observed in seven patients (15%), directly attributable to surgery in three cases. After a median follow-up of 48 months (range, 13 to 129 months), 44 patients are alive. Six children experienced local relapse; four of these children achieved subsequent remission. The projected overall survival and event-free survival (EFS) rates at 5 years are, respectively, 93% +/- 4% and 84% +/- 5%. Survival of children treated with preoperative chemotherapy are similar to those treated by primary surgery (80% and 88% respectively). The extent of surgical resection seemed to have no influence on the outcome (EFS rates 76% and 89% in case of gross residue and complete resection or microscopic residue, respectively). CONCLUSION: Our data confirm the excellent survival of localized pelvic NBs. Considering the efficacy of preoperative chemotherapy, patients with pelvic NB should be carefully screened for primary surgery. The risk of neurologic impairment during radical excision should be balanced with the good survival of children with minimal residual disease.     

Lymphocyte-predominant Hodgkin's lymphoma in children: therapeutic abstention after initial lymph node resection--a Study of the French Society of Pediatric Oncology.

PURPOSE: To clarify treatment strategy for lymphocyte-predominant Hodgkin's lymphoma (LPHL), the French Society of Pediatric Oncology initiated a prospective, nonrandomized study in 1988. Patients received either standard treatment for Hodgkin's lymphoma or were not treated beyond initial adenectomy. PATIENTS AND METHODS: From 1988 to 1998, 27 patients were available for study. Twenty-four patients were male, and median age was 10 years (range, 4 to 16 years). Twenty-two, two, and three patients had stage I, II, and III disease, respectively. Thirteen patients (stage I, n = 11; stage III, n = 2) received no further treatment after initial surgical adenectomy (SA). Fourteen patients received combined treatment (CT; n = 10), involved-field radiotherapy alone (n = 1), or chemotherapy alone (n = 3). The two groups were comparable for clinical status, treatment, and follow-up. RESULTS: Twenty-three of 27 patients achieved complete remission (CR). With a median follow-up time of 70 months (range, 32 to 214 months), overall survival to date is 100%, and overall event-free survival (EFS) is 69% +/- 10% (SA, 42% +/- 16%; CT, 90% +/- 8.6%; P <.04). If we considered only the patients in CR after initial surgery (n = 12), EFS was no longer significantly different between the two groups. Patients with residual mass after initial surgery (n = 15) had worse EFS if they did not receive complementary treatment (P <.05). CONCLUSION: Although based on a small number of patients, our study showed that (1). no further therapy is a valid therapeutic approach in LPHL patient in CR after initial lymph node resection, and (2). complementary treatment diminishes relapse frequency but has no impact on survival.     

Temozolomide in malignant gliomas of childhood: a United Kingdom Children's Cancer Study Group and French Society for Pediatric Oncology Intergroup Study.

PURPOSE: To determine the response rate of the malignant gliomas of childhood to an oral, daily schedule of temozolomide. PATIENTS AND METHODS: A multicenter, phase II evaluation of an oral, daily schedule of temozolomide (200 mg/m(2) on 5 consecutive days) was undertaken in children with relapsed or progressive, biopsy-proven, high-grade glioma (arm A) and progressive, diffuse, intrinsic brainstem glioma (arm B). Evidence of activity was defined by radiologic evidence of a sustained reduction in tumor size on serial magnetic resonance imaging scans. RESULTS: Fifty-five patients were recruited (34 to arm A and 21 to arm B) and received 215 cycles of chemotherapy. Grade 3/4 thrombocytopenia was the most frequent toxic event (7% of cycles). Prolonged myelosuppression resulted in significant treatment delays and dose reductions (17% and 22% of cycles, respectively). Two toxic deaths were documented and were related to myelosuppression and sepsis in one patient and pneumonia in a second. The overall (best) response rate was 12% for arm A (95% confidence interval [CI], 3 to 28 in the study cohort, and 2 to 31 for eligible patients) and 5% and 6%, respectively, for arm B (95% CI, 0 to 26 in the study cohort, and 0 to 27 for eligible patients). Stabilization of disease was also documented and was most noteworthy for brainstem gliomas, where two patients achieved both radiologic static disease and discontinued steroid medication. CONCLUSION: Despite moderate toxicity, objective response rates to temozolomide have been low, indicating that temozolomide has minimal activity in the high-grade gliomas of childhood.     

Treatment of stage I and II Hodgkin's disease with NOVP (mitoxantrone, vincristine, vinblastine, prednisone) and radiotherapy.

We investigated the effectiveness of a new treatment regimen termed NOVP in early Hodgkin's disease, which reportedly has lower toxicity. Thirty-four patients were treated with three cycles of NOVP (mitoxantrone, vinblastine, vincristine, prednisone) and radiotherapy, 40% of them had unfavourable prognostic factors. All patients obtained complete remission. With a median follow up of 5 years, the overall survival (OS) and time to treatment failure (TTF) was 95% (95% confidence interval [CI], 87 to 103) and 89% (95% CI, 78 to 100), respectively. The presence of either B symptoms or pulmonary hilar involvement was associated with a significant decrease in TTF (91% VS 50% p=0.003 and 92% VS 30% p=0.02, respectively) but do not correlate with OS. The tolerance to NOVP was excellent with minimal toxicity. In conclusion, this regimen is associated with a favourable outcome and low toxicity in stage I and II Hodgkin's disease, although patients with B symptoms and pulmonary hilar involvement have a higher risk of relapse.