Cost-effectiveness of first-line treatment options for patients with advanced-stage Hodgkin lymphoma: a modelling study.

BACKGROUND: Several strategies are available for the initial treatment of advanced-stage Hodgkin lymphoma, but the optimal strategy in terms of cost-effectiveness is unclear. The aim of this study was to compare the quality-adjusted effectiveness and costs of five modern treatment options for transplantation-eligible patients with newly diagnosed advanced-stage Hodgkin lymphoma. METHODS: A Markov decision-analytic model was developed using a 20-year time horizon. Five of the most common treatment approaches were selected based on clinical experience and expert opinion: (1) six cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD), including data from the HD2000 trial, Viviani and colleagues, and EORTC trial; (2) six cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP; from the HD15 trial or PET-adapted as in the HD18 trial, two initial cycles of BEACOPP followed by four additional cycles for patients with a positive PET and either two or four additional cycles of BEACOPP for patients with a negative PET); (3) PET-adapted escalation (as in the RATHL trial, two cycles of standard ABVD chemotherapy followed by an additional four cycles of ABVD or AVD in PET-negative patients and four cycles of BEACOPP in PET-positive patients); (4) six cycles of brentuximab vedotin, doxorubicin, vinblastine, dacarbazine (A-AVD) or ABVD as in the Echelon-1 trial; and (5) PET-adapted de-escalation (as in the AHL2011 trial, two cycles of BEACOPP followed by PET2 scan; PET-positive patients received two additional BEACOPP cycles and PET-negative patients received two cycles of ABVD; at PET4, PET-negative patients completed two further cycles of either ABVD or BEACOPP depending on what they received after PET2, and PET-positive patients received salvage therapy). Note that all uses of BEACOPP in these strategies were BEACOPPescalated. The randomised groups of interest from these studies comprised 4255 patients enrolled between April, 2000, and January, 2016. Baseline probability estimates and utilities were derived from the included trials in addition to a systematic review of published studies. A Canadian public health payer's perspective was considered (CAN$1=US$0·74) and adjusted for inflation for 2018. All costs and benefits were discounted by 1·5% per year because life-years now are more valuable than future potential life-years. FINDINGS: Probabilistic analyses (10 000 simulations) showed that, for a willingness-to-pay threshold of CAN$50 000, a PET-adapted de-escalation strategy based on AHL2011 was more cost-effective 87% of the time. This strategy had the highest number of life-years (14·6 years [95% CI 13·7-15·1]) and quality-adjusted life years (13·2 years [95% CI 10·2-14·4]), and the lowest direct costs ($53 129 [95% CI 31 914-94 446]) compared with the other treatment regimens. Sensitivity analyses showed that the model was robust to key variables, including probability of treatment-related mortality, relapse, frequency of secondary malignancy, death from secondary malignancy, and probability of infertility after BEACOPP. INTERPRETATION: Our results suggest that, when considering cost, effectiveness, and short and long-term toxicities, the preferred treatment strategy for patients with newly diagnosed advanced-stage Hodgkin lymphoma is the PET-adapted de-escalation regimen starting with BEACOPP and de-escalating to ABVD as appropriate. Although our findings do not provide an absolute best treatment approach for clinicians to follow for all patients, they can contribute to shared decision making between patients and treating physicians. FUNDING: None.

An evaluation of brentuximab vedotin as a treatment option for stage III/IV Hodgkin lymphoma.

Introduction: Outcomes of patients with classical Hodgkin lymphoma are excellent, and the intent of frontline therapy for even advanced-stage disease has been curative. This review summarizes the role of brentuximab vedotin in the upfront treatment of advanced stage classical Hodgkin lymphoma in the context of reducing therapy-related toxicity without compromising the high cure rate. Areas covered: Strategies to reduce bleomycin-induced lung toxicity include a response-adapted approach investigated in the RATHL study and a replacement of bleomycin with brentuximab vedotin in frontline chemotherapy regimens. In both studies, omission of bleomycin in the non-standard arms decreased the rate of pulmonary toxicity while maintaining high progression-free survival and overall survival rates. Expert opinion: The approval of A+AVD in North America offers a new bleomycin-free regimen for the treatment of advanced-stage HL, but it must be balanced against a risk-adapted approach. Recently presented subset analyses raise a question about which patients benefit most from this therapy.

[Chemotherapy in male external genital organs (testicular and penile cancer)]. / Chimiothérapie des organes génitaux externes chez l'homme (cancer du testicule et du pénis).

AIM: To describe drugs used in the chemotherapy of testis and penis neoplasms. MATERIAL: Bibliographical search was performed from the database Medline (National Library of Medicine, PubMed) and websites of the HAS and the ANSM. The search was focused on the characteristics, the mode of action, the efficiency and the side effects of the various drugs concerned. RESULTS: Nowadays, the chemotherapy is perfectly codified in adjuvant treatment or in first-line treatment of metastatic testis cancer. A single dose of carboplatin for seminoma testicular (stage I) in adjuvant treatment situation is one of the latest advances. Concerning penis cancer, the optimal protocols validated by a high level of evidence are missing. CONCLUSION: The chemotherapy in testis and penis neoplasms knew few advances in recent years. So, it is necessary to include patients in clinical research protocols.

Topical and intralesional treatment of nonmelanoma skin cancer: efficacy and cost comparisons.

BACKGROUND: Topical chemotherapy, topical immunomodulators, or intralesional chemotherapy may be used to treat nonmelanoma skin cancer (NMSC). OBJECTIVES: To review the cost and efficacy of topical and intralesional therapies for NMSC. METHODS: Literature search assessing the efficacy of NMSC treatment with topical imiquimod, topical 5-fluorouracil (5FU) intralesional 5FU, methotrexate, bleomycin, and interferon (IFN). Single-lesion case reports were excluded. Aggregate cure rates and the estimated cost of treatment (including excision and repair of recurrent lesions) for a sample 1-cm lesion on an extremity were calculated. RESULTS: Cure rates ranged from 65% to 100% for topical imiquimod and 61% to 92% for 5FU. For intralesional agents, cure rates varied considerably according to medication used and NMSC subtype treated. Keratoacanthomas had high cure rates with intralesional agents: 98% for 5FU, 91% for methotrexate, 100% for bleomycin, 100% for IFN alpha (α)-2, 83% for IFN α-2a, and 100% for IFN α-2b. Estimated costs (excluding medication cost) ranged from $205 (intralesional methotrexate for keratoacanthoma) to $1,174 (IFN α-2a for superficial basal cell carcinoma). CONCLUSION: Nonsurgical management of NMSC remains a viable and relatively cost effective treatment option in select cases. Providers should consider the relative efficacy and cost of each medication when using nonsurgical modalities.

Treatment outcome and cost-effectiveness analysis of two chemotherapeutic regimens (BEP vs. VIP) for poor-prognosis metastatic germ cell tumors.

BACKGROUND: In patients with small-volume disseminated disease of germ cell tumors, cure can be achieved with four cycles of bleomycin, etoposide, and cisplatin (BEP). However, around 20% of these cases are not curable. Strategies to improve cure rates have shown that none of the currently available modalities were superior to the others. Among the most used ones, BEP and VIP (etoposide, cisplatin, and ifosfamide) have been the most studied. However, there are no reports comparing the two, except for a few in abstract forms from southern India. Therefore, we did a treatment outcome and cost-effectiveness analysis of two chemotherapeutic regimens (BEP vs VIP) that are used in poor-prognosis metastatic germ cell tumors. MATERIALS AND METHODS: All male patients with germ cell tumors, diagnosed as having poor risk by IGCCCG, between January 2002 and December 2004 were included in the study. Clinical, laboratory, and other data were recorded. The patients were stratified into two categories on the basis of the type of chemotherapeutic regimen they received. RESULTS: In all, 46 patients were analyzed, with a median follow up of 26.6 months. The baseline characteristics (age, stage, PS, histology, and serum markers) were not different in the two treatment arms. There is no significant difference in the outcome with either of the chemotherapeutic modalities. VIP is less cost effective and more toxic compared to BEP. CONCLUSION: In view of the greater toxicity and cost of therapy, as well as lack of either overall or disease free survival advantage, VIP is not a preferred option for patients with high-risk germ cell tumors in the Indian setting and it is still advisable to treat patients with BEP.

Cost-effectiveness analysis comparing chemotherapy regimens in the treatment of AIDS-related Kaposi's sarcoma in Brazil.

BACKGROUND: Economic analyses of agents used in the treatment of AIDS and opportunistic diseases are particularly important in developing countries. PURPOSE: To analyze the cost-effectiveness of AIDS-related Kaposi's sarcoma (AIDS-KS) chemotherapy regimens in Brazil. METHOD: A decision-analysis model was developed, and effectiveness data were derived from randomized phase III trials evaluating pegylated liposomal doxorubicin (PLD), liposomal daunorubicin (DNX), and the ABV regimen (doxorubicin, bleomycin, and vincristine). Resource data on direct medical costs were obtained from local sources. RESULTS: The cost-effectiveness estimates (defined as average costs per patient who responds completely or partially) favored PLD (US $10,272/responder) in comparison to DNX (US $16,263/responder). Regarding cost-effectiveness, the ABV regimen that is widely used in developing countries had better results when compared to both PLD (US $1,268 vs. US $10,271) and DNX (US $1,268 vs. US $16,260). The incremental cost per additional responder of using PLD instead of ABV was US $20,990. Sensitivity analyses suggest that these results hold over a wide range of assumptions. CONCLUSION: ABV seems to be the most reasonable treatment option for AIDS-KS patients in resource-limited countries like Brazil.

Prospective randomized trial of talc slurry vs bleomycin in pleurodesis for symptomatic malignant pleural effusions.

OBJECTIVE: Symptomatic malignant pleural effusions are common sequelae in patients with certain malignancies. Pleurodesis via bedside thoracostomy is the current treatment option most commonly used. To our knowledge, this is the first prospective randomized trial to examine which agent, bleomycin or talc slurry, is superior in terms of effectiveness, safety, and cost. PATIENTS AND METHODS: Between July 1992 and March 1995, 35 patients presenting to our medical center with symptomatic malignant pleural effusions were prospectively randomized to undergo chemical pleurodesis with either bleomycin or talc slurry via bedside thoracostomy. The conditions of patients were assessed and graded before and after treatment concerning pain, dyspnea, and chest radiographs. RESULTS: Twenty-nine patients who underwent 33 treatments (14 with bleomycin and 19 with talc) were available for follow-up. Follow-up ranged from 2 weeks to 8 months (mean, 1.7 months). Both groups demonstrated notable improvement in both pain and dyspnea following treatment, but there were no statistically significant differences between groups in the amount of improvement (two-tailed Student's t test). Permanent control of effusions, defined objectively on chest radiograph, was achieved with 11 bleomycin treatments (79%) and 17 talc treatments (90%) (p=0.388). The procedures were well tolerated and no significant adverse effects were observed. Talc is a much less costly agent than bleomycin ($12.36 cost to our medical center per treatment for talc vs $955.83 for bleomycin). CONCLUSION: Given the similar efficacy and significant cost advantage, we conclude that talc is the agent of choice when utilizing pleurodesis for control of symptomatic malignant pleural effusions.

Sclerotherapy for malignant pleural effusions: alternatives to tetracycline.

Malignant pleural effusion (MPE) causes significant morbidity in cancer patients. Management is often challenging because of the recurrent nature of MPE and the inconsistent response rates of various treatments. In patients whose underlying malignancy is unresponsive to systemic chemotherapy or radiation, MPE is usually managed by tube thoracostomy with subsequent sclerotherapy. Selection of a sclerosing agent should be based on several factors, including efficacy, toxicity, cost, and convenience. Of the numerous agents available for managing MPE, doxycycline, bleomycin, and talc have emerged as the most promising. Even these agents have disadvantages, such as the high cost of bleomycin and the possible need for multiple dosing of doxycycline. Talc is clearly the most controversial of the three. Although its efficacy is well documented, its role remains unclear because of its unattractive side effect profile and inconvenient preparation and administration. Results of controlled comparative trials are needed to identify the optimal sclerosing agent.