Treatment Of First Relapse Research Articles

Real-world direct healthcare costs of treating recurrent high-grade serous ovarian cancer with cytotoxic chemotherapy.

Aim: To describe the direct healthcare costs associated with repeated cytotoxic chemotherapy treatments for recurrent high-grade serous cancer (HGSC) of the ovaries. Patients & methods: Retrospective review of 66 women with recurrent stage III/IV HGSC ovarian cancer treated with repeated lines of cytotoxic chemotherapy in a Canadian University Tertiary Center. Results: Mean cost of treatment of first relapse was CAD$52,227 increasing by 38% for two, and 86% for three or more relapses with median overall survival of 36.0, 50.7 and 42.8months, respectively. In-hospital care accounted for 71% and chemotherapy drugs accounted for 17% of the total costs. Conclusion: After the third relapse of HGSC, cytotoxic chemotherapy did not prolong survival but was associated with substantially increased healthcare costs.

Carfilzomib Versus Bortezomib in Combination with Cyclophosphamide and Dexamethasone for Treatment of First Relapse or Primary Refractory Multiple Myeloma (MM): Outcomes Based on Genetic Risk and Long Term Follow up of the Phase 2 Muk Five Study

Carfilzomib Versus Bortezomib in Combination with Cyclophosphamide and Dexamethasone for Treatment of First Relapse or Primary Refractory Multiple Myeloma (MM): Outcomes Based on Genetic Risk and Long Term Follow up of the Phase 2 Muk Five Study

Comparative efficacy of multiple myeloma therapies for treatment of first relapse: A systematic literature review and network meta-analysis.

8042 Background: Treatment for multiple myeloma (MM) in the US has undergone significant advances, with several new therapies recently FDA approved for relapse/refractory MM (RRMM), including carfilzomib+lenalidomide+dex (KRd), carfilzomib+dex (Kd), daratumumab+lenalidomide+dex (DRd), daratumumab+bortezomib+dex (DVd), ixaxomib+lenalidomide+dex (IRd), and elotuzumab+lenalidomide+dex (ERd). These new therapies have shown improvements in clinical outcomes in randomized controlled trials (RCTs). However, with few head-to-head RCTs, there is little comparative evidence to determine the most effective treatment for specific patients. A systematic literature review (SLR) and network meta-analysis (NMA) was conducted to determine the comparative efficacy (progression free survival (PFS)) of MM therapies for treating first relapse. Methods: The SLR searched MEDLINE, Embase, and the Cochrane Library for RCTs investigating the efficacy of treatments for RRMM (to August 2016). NMA was conducted on the PFS hazard ratios (HR), where available in RCTs for patients with one prior line of treatment, using Bayesian fixed effects mixed treatment comparisons. Results: Data formed two evidence networks. Network 1: RCTs with Rd; Network 2: RCTs with Vd. Analyses found DRd and DVd had the highest probability of being the best treatment (0.96 and 0.89, respectively). Compared to other MM therapies, DRd and DVd had the lowest risk of progression or death (PFS HR <1.0) (Table 1). For example, compared to KRd, DRd had a 41% (PFS HR 0.59) reduced risk of progression or death. Conclusions: This analysis provides comparative evidence among treatments where head-to-head RCTs have not been conducted. For treating first relapse, compared to other MM treatments, this analysis found that DRd and DVd had the highest probability of providing the longest progression free survival. [Table: see text]

Low-Dose Radiotherapy in Patients with Non Hodgkin Lymphoma

AbstractAbstract 4875 Background:Some studies have showed high activity for low-dose radiotherapy (LDRT) in low-grade Non-Hodgkin Lymphoma (NHL). However, this therapeutic approach is often forgotten and other approaches are used - chemotherapy and/or conventional radiotherapy - associated with greater toxicity. The efficacy of total body LDRT (1.5–2 Gy, fractions 0.1–0.25 Gy in 2 – 5 times a week) in disseminated disease is associated with 10 year progression free survival (PFS) of 15 – 25%, with response rates of 70 – 90% (Gérard et al., IJ Radiation Oncology 2010; 78), despite hematologic toxicity and leukemogenic effects. Although its mechanism of action is unknown, its effectiveness has been confirmed (Jones et al., Cancer 1973; 32) suggesting that low dose radiation induces localized lymphocytes apoptosis that can trigger local and systemic benefits. More recently, LDRT was used in palliative treatment for patients with localized disease (4Gy into two fractions, for 3 days) with a low toxicity, and with an objective response (partial or complete) in 24/37 patients, 89% (G Ganem et al., Hematol Oncol1997; 42). Objectives:To assess the response to treatment with LDRT. Explore the predictive factors of response. Determine the progression-free survival (PFS) after LDRT. We will present PFS after LDRT and compare PFS in second line treatment: LDRT vs convencional chemotherapy. Methods:Retrospective study of 44 patients with new or recurrent NHL, treated with LDRT (4Gy in 2 fractions) in 1stor more lines, in a cancer care centre between 2004 and 2011.All transformed lymphomas were excluded (4 patients), as well all diagnosis that weren't centrally reviewed. Patients with complete resolution of the disease according to clinical and/or image studies were considered to have achieved complete response (CR). Results:We identified 40 patients undergoing LDRT, with a median follow-up of 69,5 months after LDRT ([28–87]). 52,5% (n = 21) were male, median age at the time of LDRT was 69 years ([31–85]). 75% of patients (n = 30) had follicular NHL, 12,5% (n = 5) Mantle cell NHL, 10% (n = 4) Marginal Zone NHL and 2,5% (n = 1) lymphoplasmacytic lymphoma.The median numbers of lines of chemotherapy completed before LDRT were 2 lines ([0–5]). There wasn’t any impact on PFS on using Rituximab containing regimens after LDRT (p> 0,05). The overall response rate to LDRT was 92,5% (n = 37): 42,5% (n = 17) achieved complete response (CR), 50% (n = 20) partial response (PR) and 7,5% (n = 3) had disease progression. There weren’t any treatment related toxicities, nor was histological transformation recorded after treatment with LDRT. The logistic regression analysis showed that irradiated areas with dimension <40mm are an independent predictive factor of response (p <0,031, 95% CI [1,268-133,285]). We find a median PFS of 4 months ([0–72]) for patients that went on LDRT, and 50% of these patients relapsed after a median 5 months ([0–35]). 56,5% (n = 13) showed relapse at the same location of the irradiated area. Patients who have completed one chemotherapy scheme after relapsing following LDRT, showed a rate of 6 months-PFS of 50% such as the patients that have done a second LDRT treatment.Concerning follicular NHL patients who relapsed after 1st line conventional chemotherapy, 43,8% (n = 7) were treated with LDRT and 56,2% (n = 9) were treated with conventional 2nd line chemotherapy. Comparing these two groups of patients, there weren’t any difference for PFS for both groups (mean 9,5 vs 9 months p> 0,05, for LDRT vs 2ndline chemotherapy), for equal overall survival. Conclusion:LDRT is an effective treatment for patients with relapsed or recurrent advanced stage NHL. We can obtain high response rates with negligible toxicity. In the treatment of first relapse, PFS is similar when using LDRT or 2nd line chemotherapy. Considering that Rituximab promotes a synergistic effect with LDRT-induced apoptosis and decrease the cell turnover (Skvortsova I et al., J Radiat Res (Tokyo) 2006), comparative studies with conventional chemotherapy regimens should be promoted. Treatment with conventional radiotherapy should be used in patients with relapsed low-stage and localized disease, having curative intention or locally controlling involved areas. Disclosures:No relevant conflicts of interest to declare.

Outcome of High-Risk and Refractory AML/MDS Patients Receiving a FLAMSA Sequential Chemotherapy Regimen Followed by Reduced-Intensity Conditioning (RIC) and Allogeneic Hematopoeitic Stem Cell Transplantation (allo-HSCT)

Abstract 1957▪▪This icon denotes a clinically relevant abstract Introduction:The FLAMSA sequential chemotherapy regimen followed by RIC for allo-HSCT and prophylactic donor lymphocyte transfusion (pDLT) was introduced a few years ago as a salvage therapy for patients with refractory or high risk AML/MDS. This retrospective analysis aimed to assess the outcome of 40 patients with refractory or high risk AML/MDS who received a salvage FLAMSA sequential chemotherapy (including a subgroup of patients who received a modified FLAMSA regimen incorporating Busulfan instead of total-body irradiation (TBI)). Patients and methods:This series included 30 males and 10 females with a median age of 52 years (range, 32–66) treated in 2 transplant centres in France. Diseases characteristics were as follow: progressive or refractory disease after rescue treatment for first relapse (n=21), early relapse without any further salvage therapy (n=4), and primary induction failure (PIF; n=4). The series also included 7 patients with high risk MDS (IPSS ≥ 1.5), and another 4 patients in first CR but having a very poor prognosis based on cytogenetics features (CR group hereinafter). According to cytogenetics and molecular markers, 12 patients were classified in the “standard risk” cytogenetics risk group, while 21 patients had an unfavourable/poor profile. Data were not available for 7 patients.The FLAMSA regimen included Fludarabine (30 mg/m2/d), cytarabine (2 g/m2/d) and amsacrine (100mg/m2/d) from day −12 to day −9. In addition, priming with G-CSF once daily was done in 12 patients. After 3 days of rest, a RIC regimen was administered. In 28 patients, the RIC regimen included 4 Gy. TBI, ATG 5 mg/kg total dose, and cyclophosphamide (40 mg/kg in case of matched related donors, and 60 mg/kg for unrelated or mismatched donors). In the remaining 12 patients, TBI was replaced by I.V. Busulfan 3.2 mg/kg/d for 4 days. Per protocol, pDLT was planned to be given from day +120 in patients who were not receiving immunosuppression and were free of GvHD. Eighteen patients were transplanted using an HLA identical sibling donor, and 22 received transplant from an unrelated donor (14 matched 10/10 and 8 mismatched 9/10). Results:After allo-HSCT, 39 patients (97.5%) engrafted. In the CR group (n=4), after a median follow-up of 5 months (range, 3–31) all patients were still alive in CR at last follow-up. In the remaining 36 patients, 9 patients developed acute GVHD ≥2 with a cumulative incidence at 3 months of 18% (95%CI, 10–26). At day 90 post HSCT, 23 (64%) patients could achieve hematological CR, and 14 of the 23 remained in CR at last follow-up.After a median follow-up of 6 months (range, 1–60), the 2-years probability of OS was 30% (95%CI, 17–52), and the 2-years probability of PFS was 29% (95%CI, 17–50). The cumulative incidence of disease progression at 1 year was 25% (95%CI, 18–33). Interestingly, none of the patients who received Busulfan instead of TBI as part of the RIC, relapsed. The cumulative incidence of TRM at 3 months and 1 year were 14% (95%CI, 8–20) and 22% (95%CI, 15–29), respectively.In the multivariate analysis (taking into account all relevant parameters such as priming with G-CSF, conditioning with or without TBI, related or unrelated donors, HLA matching and number of previous treatment lines), there was a significantly worsened PFS in patients who received transplant from a mismatched donor (HR=3.6; [95%CI, 1.3–10] p=0.01; below Figure). Also, when considering disease relapse, there was a highly significant impact of the type of RIC regimen (in favour of a FLAMSA regimen without TBI (p<0.0001, Figure). Conclusion:Despite its limitations, results from this analysis confirm that a FLAMSA sequential chemotherapy regimen followed by RIC and allo-HSCT is a valid salvage therapy for patients with refractory or high risk AML/MDS. This study shows that HLA mismatched donors should be avoided in FLAMSA regimen. Moreover a modified FLAMSA regimen incorporating I.V. Busulfan instead of TBI is likely to allow better long-term disease control, warranting prospective evaluation. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Role of Reduced-Intensity Conditioning Followed by Allogeneic Stem Cell Transplantation In Patients with Multiple Myeloma Relapsing After Autograft: a Donor Versus No Donor Analysis

AbstractAbstract 3534 Background:Allogeneic stem cell transplantation (allo-SCT) employing reduced intensity conditioning (RIC) is a feasible procedure in selected patients with relapsed multiple myeloma (MM), but its efficacy is still a matter of debate. The mortality and the morbidity related to the procedure and the rather high relapse risk have made the use of allo-SCT controversial. In addition, the availability of novel anti myeloma treatments, such as bortezomib and lenalidomide, have made the use of allo-SCT less appealing for clinicians. Aims:We investigated the role of RIC allo-SCT in MM pts who relapsed after autologous stem cell transplantation (auto-SCT) and were then treated with a salvage therapy based on novel agents. Our study was structured similarly to an intention to treat analysis and included only those pts undergoing a HLA-typing immediately after the failure of auto-SCT. The cohort of pts having a donor (donor group) was compared with the one not having a suitable donor (no donor group). Patients and methods:One hundred sixty-nine consecutive pts were retrospectively evaluated in a multicenter study between 2002 and 2008. Seventy-five found a donor and 68 (90%) underwent an allo-SCT: 24 identical sibling (35%), 44 MUD (75%). Conditioning regimens were fludarabine, melphalan±thiotepa in 28 patients (41%), fludarabine + 2 Gy TBI in 24 cases (35%), fludarabine and cyclophosphamide in 8 patients (12%) and fludarabine and treosulfan in the remaining 8 cases (12%). Seven pts having a donor did not receive allo-SCT for progressive disease or severe comorbidities. Median age of donor group was significantly younger than no donor group (53 versus 59 years, p<0.0001). No significant differences were detected between the donor and no donor groups with regard of high-risk karyotype at diagnosis (40% vs 43%), median time between auto-SCT and relapse (15 vs 17 months), treatment of first relapse (thalidomide-based 52% vs 39%, bortezomib-based 33% vs 33%, lenalidomide 8% vs 18%, other therapies 7% vs 10%), median duration of first salvage treatment (4 versus 5 months) and quality of response after treatment of first relapse (CR + VGPR 33% versus 29%, PR 47% vs 32%, SD 12% vs 19%, PD 8% vs 20%). Results:The median follow-up after the beginning of first salvage treatment was 19 months (1-97) for all patients and 29 months for living patients. Two-year cumulative incidence of non relapse mortality (NRM) was 22% in the donor group and 1% in the no-donor group (p<0.0001). Two-year cumulative incidence of relapse was 43% in the donor group and 81% in the no donor group(p< 0. 01). Two-year PFS was 32% in the donor-group and 12% in the no-donor group(p< 0.0001). Two-year OS was 43% in the donor-group and 34% in the no-donor-group (p=0.323). In multivariate analysis, the unavailability of a donor was a significant unfavourable factor for PFS (HR 2.56; 95% CI, 1.35–4.85), but not for OS. Moreover, high-risk karyotype at diagnosis and lack of chemo-sensitivity after salvage treatment significantly reduced both PFS (HR 6.80; 95% CI, 2.19–21.07 and HR 2.27; 95% CI, 1.35–21.07, respectively) and OS (HR 2.37; 95% CI, 1.13–4.96 and HR 3.81; 95% CI, 1.76–8.23, respectively). In patients who actually underwent RIC allo-SCT, the development of chronic GVHD was the only factor that was significant for both EFS and OS in univariate analysis (HR 0.39; 95% CI, 0.16–0.94 and HR 0.30; 95% CI, 0.10–0.91, respectively). Conclusions:This study comparing salvage treatment with novel agents consolidated by RIC allo-SCT versus salvage treatment alone after a failed auto-SCT provides evidence for a significant PFS benefit in MM patients having a donor. However, we could not detect a OS advantage. The protective effect of chronic GVHD in transplanted patients indicated a possible role of graft-versus-myeloma effect. These results suggest that allo-SCT is still a reasonable option in young patients with relapsed myeloma having a donor, but new transplant strategies that will reduce NRM and novel agents as consolidation/maintenance after allo-SCT have to be investigated. Disclosures:No relevant conflicts of interest to declare.

The Association of a Salvage Treatment Containing Novel Agents Followed by Allogeneic Stem Cell Transplantation with Reduced-Intensity Conditioning Regimen Improves Overall Survival and Time-to-Progression in Multiple Myeloma Patiens Relapsing After Autologous Stem Cell Transplantation: A Multicentric Retrospective Study Based On Donor Availability.

Abstract 4320 BackgroundSalvage treatments containing thalidomide, lenalidomide or bortezomib can induce a response rate in 30 to 60% of multiple myeloma (MM) patients (pts) relapsing after single or tandem autologous transplantation (auto-SCT) with a median response duration between 6 and 12 months. However, long-term disease control or cure cannot be commonly achieved. Allogeneic stem cell transplantation (allo-SCT) employing reduced intensity conditioning (RIC) has been increasingly performed in MM, but its efficacy in this clinical setting is still a matter of debate. AimsWe investigated the role of RIC allo-SCT in MM pts who relapsed after auto-SCT and were then treated with a salvage therapy based on novel agents. In order to limit any selection bias, our study was structured similarly to an intention to treat analysis and included only those pts undergoing a HLA-typing immediately after the failure of auto-SCT. The cohort of pts having a donor (donor-group) was compared with the one not having a suitable donor (no-donor group). Patients and methodsOne hundred thirty–six consecutive pts were retrospectively evaluated in a multicenter study. Fifty-seven found a donor and 50 (88%) underwent an allo-SCT: 16 identical sibling (32%), 34 MUD (68%). Conditioning regimens were fludarabine, melphalan±thiotepa in 21 patients (42%), fludarabine + 2 Gy TBI in 15 cases (30%), fludarabine and cyclophosphamide in 8 patients (16%) and fludarabine and treosulfan in the remaining 6 cases (12%). Seven pts having a donor did not receive allo-SCT for progressive disease or severe comorbidities. Median age of donor-group was significantly younger than no-donor group (53 versus 60 years, p=0,000045). No differences were detected between the donor and no-donor group with regard of median time between auto-SCT and relapse (17 months in both groups), treatment of first relapse (thalidomide-based 55% vs 31%, bortezomib-based 35% vs 46%, lenalidomide 10% vs 23%), median duration of salvage treatment (4,5 months versus 4 months) and percentage of responsive patients after treatment of first relapse (CR + VGPR 37% versus 30%, PR 46% vs 34%, SD 12% vs 18%, PD 5% vs 18%). ResultsThe median follow-up for all patients was 15 months (1-97) after relapse. The median time to progression (TTP) and overall survival (OS) for all patients were 16 and 25 months, respectively. Two-year TTP was 55% in the donor-group and 18% in the no-donor group (p<0.00001). Two-year OS was 57% in the donor-group and 48% in the no-donor group (p=0.004). In univariate analysis the availability of a donor and a duration of salvage treatment longer than 6 months significantly prolonged TTP (p=0.002 and p=0.008, respectively), while the availability of a donor and time from auto-SCT to relapse longer than 12 months significantly prolonged OS (P=0.009 and p=0.007, respectively). The 50 patients that actually proceeded to allo-SCT had a 1-year TRM of 8% and a 2-year TTP and OS of 53 % and 57%, respectively. Acute GVHD grade II-IV occurred in 19 patients (38%) and chronic GVHD in 14 patients (28%). In univariate analysis TTP was significantly prolonged for patients who were transplanted from sibling donors and for those who relapsed after at least 12 months after auto-SCT (p= 0.01 and p=0.05 respectively). ConclusionsWe conclude that the association of a salvage treatment containing novel agents consolidated by RIC allo-SCT seems a feasible strategy with a rather low mortality and an encouraging TTP and OS in patients relapsing after auto-SCT. Both availability of a donor as well as late (>12 months) relapse from auto-SCT positively impacted on OS. Disclosures:Einsele:celgene: Research Funding; orthobiotech: Research Funding.

Improved Relapse Free Survival Is Predicted by a Negative Pre-Transplant FDG-PET Scan Following Salvage Chemotherapy for Relapsed Diffuse Large B Cell Lymphoma (DLBCL) Treated with Autologous Stem Cell Transplantation.

Introduction FDG-PET imaging is a powerful predictor of both positive and negative outcome of initial therapy for DLBCL. Existing data on the utility of PET to predict outcome of ASCT have included a range of histological subtypes, limiting its direct applicability to the setting of DLBCL.Methods Data from 41 consecutive patients who had PET scans immediately prior to undergoing ASCT for treatment of first relapse of de novo DLBCL were analysed. We compared the clinical characteristics, event free survival (EFS) and overall survival (OS) of those with residual FDG avid disease (n=21) against those without FDG avid disease (n=20).Results The median age was 53(18–71). Patient characteristics are shown in the table. At 3 years, the OS was 67(±8)%, and the EFS was the 62(±8)%. EFS for PET positive patients was 38(±12)% vs 79(±9%) for PET negative patients (p=0.04). OS was 37(±17%) vs 81(±10%) (p=0.08) respectively.Conclusion Excellent EFS and OS can be anticipated from ASCT when undertaken in those who have achieved a PET negative remission following salvage chemotherapy. Conversely, failure to achieve a PET negative remission after salvage chemotherapy in relapsed DLBCL predicts for a poorer, but not irretrievable outcome after ASCT, suggesting that a proportion of PET positive patients can be successfully salvaged by either ASCT or post-ASCT salvage therapies.Patient CharacteristicsPET Positive (n=21) PET negative (n=20)PET negative (n=20)Female28%40%Median Age (Range)53 (28–65)53(81–71)Salvage RegimenICE ±R 66%ICE ±R 80%Conditioning RegimenBEAM 47%, SBCNU 23% BuMel 14% other 16%BEAM 25%, SBCNU 25% , BuMel 25% other 25%Rituximab with salvage71%95%Rituximab in initial therapy33%25%RT with salvage or ASCT43%25%

Single-agent thalidomide for treatment of first relapse following high-dose chemotherapy in patients with multiple myeloma

Single-agent thalidomide for treatment of first relapse following high-dose chemotherapy in patients with multiple myeloma

Moving disease biology from the lab to the clinic.

Multiple myeloma (MM) cells home to and adhere to extracellular matrix proteins and to bone marrow stromal cells (BMSCs); and in the BM microenvironment, grow, survive, resist drugs, and migrate under the influence of cytokines including interleukin-6, vascular endothelial growth factor, tumor necrosis factor alpha, and insulin-like growth factor (IGF)-1. Proliferation is via the Ras/Raf MAPK cascade, drug resistance via PI3-K/Akt signaling, and migration via PKC dependent pathways. Novel therapies that target not only the MM cell, but also the BM microenvironment, can overcome drug resistance in vitro and in vivo in murine human MM models. For example, immunomodulatory derivatives of thalidomide (IMiDs) and the proteasome inhibitor PS-341 both induce apoptosis of MM cell lines and patient cells refractory to melphalan, doxorubicin, and dexamethasone; abrogate MM cell binding to fibronectin and BMSCs and related protection against immune- and drug-induced apoptosis; block production of cytokines which promote MM cell growth, survival, drug resistance, and migration; inhibit angiogenesis; and stimulate host anti-tumor immunity. In the setting of relapsed refractory MM, a Phase I trial of the IMiD CC5013 shows stable paraprotein or better in 20 of 24 (79%) patients, with a favorable toxicity profile. In this same patient population 85% of 54 patients treated in a Phase II trial of PS-341 achieved either paraprotein response (50%) or stable disease (35%). Cellular and gene microarray studies comparing PS-341 and an IkappaB kinase inhibitor, PS-1145, suggest that selective NF-kappaB blockade cannot account for all the anti-MM activity of PS-341. Finally, cellular and signaling studies provide the preclinical rationale for combining these novel agents with conventional therapies, or with each other, to enhance efficacy. These novel therapeutics therefore represent a new treatment paradigm in MM targeting the tumor cell in its microenvironment to overcome classical drug resistance and improve patient outcome. Future studies should define the utility of these agents as primary therapy, treatment for first relapse, and maintenance therapy.

Duration of hospitalization as a measure of cost on Children's Cancer Group acute lymphoblastic leukemia studies.

We used duration of hospitalization as a surrogate for cost and event-free survival as a measure of effectiveness to estimate the cost-effectiveness ratios of various treatment regimens on Children's Cancer Group trials for acute lymphoblastic leukemia. The analyses included 4,986 children (2 to 21 years of age) with newly diagnosed acute lymphoblastic leukemia enrolled onto risk-adjusted protocols between 1988 and 1995. Analyses were based on a model of 100 patients. The marginal cost-effectiveness ratio (hospital days per additional patient surviving event-free) was the difference in total duration of hospitalization divided by the difference in number of event-free survivors at 5 years for two regimens. Relapse-adjusted marginal cost of frontline therapy was the difference in total duration of hospitalization for frontline therapy plus relapse therapy divided by the difference in number of event-free survivors at 5 years on the frontline therapy for two regimens. One or two delayed intensification (DI) phases, augmented therapy, and dexamethasone all improved outcome. Marginal cost-effectiveness of these regimens compared with the control regimens was 133 days per patient for DI, 117 days per patient for double DI, and 41 days per patient for augmented therapy. Dexamethasone resulted in 17 fewer days per patient. Relapse-adjusted marginal costs were 68 days per patient for DI and 52 days for double DI. Augmented therapy and dexamethasone-based therapy resulted in 16 and 82 fewer hospital days, respectively. The estimated cost-effectiveness for treating any first relapse was 250 days per patient. DI, double DI, augmented therapy, and dexamethasone-based therapy are cost-effective strategies compared with current treatment of first relapse.

Combination of rubidazone and cytosine arabinoside in the treatment of first relapse in acute myelocytic leukemia

This study tested the efficacy of rubidazone and cytosine arabinoside in 35 patients (13 children and 22 adults) with acute myelocytic leukemia in first relapse. Induction consisted of 1-2 courses of rubidazone 200 mg/m2 days x 4 days plus cytosine arabinoside 100 mg/m2 x 7 days in CI followed by 2 consolidation courses of 3 days and 5 days. Nineteen patients (54%) achieved complete remission, 8 failed to respond, and 8 died. Twelve patients relapsed after 1 to 9 months, at a median of 4 months, 1 patient died of cardiac failure and 1 remains in complete remission at 12 months. Five patients underwent bone marrow transplantation, 3 of them autologous, 1 was still in complete remission at 29 months, 1 relapsed, and 1 died of sepsis. Two received allogeneic marrow transplants and died at 3 and 4 months afterwards of VOD and graft failure. The main toxicity was severe and prolonged myelosuppression.

Outcome of treatment of first relapse of Hodgkin's disease after primary chemotherapy: identification of risk factors from the British Columbia experience 1970 to 1988

The outcome of treatment for a first relapse of Hodgkin's disease after primary chemotherapy was analyzed in 80 patients. They were divided into four groups: group 1 (n = 24) had initially been treated with three cycles of (mechlorethamine, vincristine, prednisone, and procarbazine [MOPP]) and wide-field irradiation therapy; group 2 (n = 25) had six cycles of MOPP; group 3 (n = 15) and group 4 (n = 16) both initially received MOPP/ABVD (MOPP plus doxorubicin, bleomycin, vinblastine, and dacarbazine) or MOPP/ABV hybrid, but group 3 received conventional salvage regimens whereas group 4 was treated with high- dose chemotherapy and autologous bone marrow transplantation as salvage therapy (n = 16). Freedom from second failure (FF2F) was used as the major endpoint. Actuarial FF2F for all patients was 38% after a median follow-up of 75 months for patients who were alive. Risk factor analysis was performed on the 71 patients who had been treated with curative intent. The presence or absence of any one of three risk factors had a strong negative impact on outcome: stage IV disease at primary diagnosis, B symptoms at relapse, or a time from primary treatment to relapse of less than 1 year. Actuarial FF2F at 5 years was 17% in the group of patients with one or more of these three factors present (n = 49). If none of these factors was present, FF2F was 82% (n = 22) (P less than .001). Even high-dose chemotherapy and autologous bone marrow transplantation were not able to overcome the negative impact of one or more risk factors (FF2F = 19%, n = 12). The outcome of salvage treatments depends most on the presence or absence of these three risk factors and less on the type of salvage treatment. Patients with none of these risk factors present have an excellent outcome if they are treated with non-cross-resistant chemotherapy, or radiotherapy, or both. Novel approaches are needed for patients with one or more of these factors present. Reports on salvage treatments for Hodgkin's disease in first relapse after primary chemotherapy should include data on the proportion of patients having stage IV disease at diagnosis, B symptoms at relapse, and a time from primary treatment to relapse of less than 1 year.

Outcome of Treatment of First Relapse of Hodgkin’s Disease After Primary Chemotherapy: Identification of Risk Factors From the British Columbia Experience 1970 to 1988

The outcome of treatment for a first relapse of Hodgkin’s disease after primary chemotherapy was analyzed in 80 patients. They were divided into four groups: group 1 (n = 24) had initially been treated with three cycles of (mechlorethamine, vincristine, prednisone, and procarbazine [MOPP]) and wide-field irradiation therapy; group 2 (n = 25) had six cycles of MOPP; group 3 (n = 15) and group 4 (n = 16) both initially received MOPP/ABVD (MOPP plus doxorubicin, bleomycin, vinblastine, and dacarbazine) or MOPP/ABV hybrid, but group 3 received conventional salvage regimens whereas group 4 was treated with high-dose chemotherapy and autologous bone marrow transplantation as salvage therapy (n = 16). Freedom from second failure (FF2F) was used as the major endpoint. Actuarial FF2F for all patients was 38% after a median follow-up of 75 months for patients who were alive. Risk factor analysis was performed on the 71 patients who had been treated with curative intent. The presence or absence of any one of three risk factors had a strong negative impact on outcome: stage IV disease at primary diagnosis, B symptoms at relapse, or a time from primary treatment to relapse of less than 1 year. Actuarial FF2F at 5 years was 17% in the group of patients with one or more of these three factors present (n = 49). If none of these factors was present, FF2F was 82% (n = 22) (P < .001). Even high-dose chemotherapy and autologous bone marrow transplantation were not able to overcome the negative impact of one or more risk factors (FF2F = 19%, n = 12). The outcome of salvage treatments depends most on the presence or absence of these three risk factors and less on the type of salvage treatment. Patients with none of these risk factors present have an excellent outcome if they are treated with non–cross-resistant chemotherapy, or radiotherapy, or both. Novel approaches are needed for patients with one or more of these factors present. Reports on salvage treatments for Hodgkin’s disease in first relapse after primary chemotherapy should include data on the proportion of patients having stage IV disease at diagnosis, B symptoms at relapse, and a time from primary treatment to relapse of less than 1 year.

Recurrent intracranial ependymomas in children survival, patterns of failure, and prognostic factors

Thirty-six pediatric patients (ages 0.8-16.8 years) with recurrent intracranial ependymoma were treated for a total of 52 separate cases of relapse from 1970 to 1989. Therapy consisted of surgery in 33 cases and chemotherapy in 38 cases. Twelve patients received radiation at the time of first relapse, and five of these 12 who had initially been treated with surgery and chemotherapy alone were irradiated to full dose. The 2-year actuarial survival and progression-free survival (PFS) rates are 29% and 23%, respectively. Two-year survival after treatment of first relapse is 39%. Of the 52 cases, there have been 44 subsequent relapses (and one septic death), three of which have occurred in the five patients treated with definitive radiation. Twenty-seven relapses have occurred exclusively with local disease. Eight patients failed with disease outside as well as in the primary site. Survival was better for patients who had histologically benign lesions at relapse (53% versus 9%, P less than 0.02), and for patients in first versus subsequent relapse (p less than 0.005). Cisplatin and etoposide (VP-16) appeared to be the most active chemotherapeutic agents. The authors conclude that some patients with histologically benign ependymoma at first relapse may benefit from aggressive therapy, with occasional long-term, progression-free survival possible. Patients with malignant lesions, or patients who relapse a second time, are less likely to benefit from conventional therapy for a significant period of time.

ADJUVANT TAMOXIFEN IN THE MANAGEMENT OF OPERABLE BREAST CANCER: THE SCOTTISH TRIAL: Report from the Breast Cancer Trials Committee, Scottish Cancer Trials Office (MRC), Edinburgh

In a trial that began in 1978, 1312 evaluable patients under 80 years of age who either had negative axillary nodes or were postmenopausal with positive axillary nodes were randomised to receive adjuvant tamoxifen 20 mg daily for 5 years, or tamoxifen for the treatment of first relapse. Estimates of oestrogen receptor (ER) content of primary tumour specimens were made in 57%. There has been a highly significant delay in relapse in the adjuvant arm of the trial. This benefit supersedes that from tamoxifen given as treatment for recurrent disease in control-arm patients (93% received this) so that benefit from adjuvant tamoxifen was maintained in the overall survival comparisons. This improvement seems to be independent of nodal and menopausal status. It does not differ significantly with ER level, although the greatest benefit in disease-free survival is in patients with levels of 100 fmol/mg protein or more.