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This manuscript describes the Advanced Breast Cancer (ABC) international consensus guidelines updated at the last two ABC international consensus conferences (ABC 6 in 2021, virtual, and ABC 7 in 2023, in Lisbon, Portugal), organized by the ABC Global Alliance. It provides the main recommendations on how to best manage patients with advanced breast cancer (inoperable locally advanced or metastatic), of all breast cancer subtypes, as well as palliative and supportive care. These guidelines are based on available evidence or on expert opinion when a higher level of evidence is lacking. Each guideline is accompanied by the level of evidence (LoE), grade of recommendation (GoR) and percentage of consensus reached at the consensus conferences. Updated diagnostic and treatment algorithms are also provided. The guidelines represent the best management options for patients living with ABC globally, assuming accessibility to all available therapies. Their adaptation (i.e. resource-stratified guidelines) is often needed in settings where access to care is limited., Competing Interests: Declaration of competing interest Matti S. Aapro: Consultant for Accord Pharmaceuticals, Amgen, BMS, Celgene, Clinigen Group, Daiichi Sankyo, Eisai Co.Ltd, Eli Lilly, Genomic Health (Exact Sciences), G1 Therapeutics, Inc., GlaxoSmithKline (GSK), Helsinn Healthcare SA, Hospira (Pfizer), Johnson & Johnson, Merck, Merck Serono (Merck KGaA), Mundipharma International Limited, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz, Tesaro (GSK), Teva Pharmaceuticals Industries Ltd., Vifor Pharma. Received honoraria for lectures at symposia of Accord Pharmaceuticals, Amgen, Astellas, Bayer HealthCare Pharmaceuticals (Schering), Biocon, Boeringer Ingelheim, Cephalon, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Eisai Co., Ltd., Dr Reddy's Laboratories, Genomic Health (Exact Sciences), Glenmark Pharmaceuticals Limited, GSK, Helsinn Healthcare SA, Hospira (Pfizer), Ipsen, Janssen Biotech, Kyowa Kirin Group, Merck, Merck Serono (Merck KGaA), Mundipharma International Limited, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz, Sanofi, Tesaro (GSK), Taiho Pharmaceutical, Teva Pharmaceutical Industries Ltd., Vifor Pharma. Grant/Research supports: Amgen, Eisai, Genomic Health (Exact Sciences), Helsinn, Hospira, Novartis, Merck, Mundipharma, Pfizer, Roche, Sandoz, Tesaro, Teva, Vifor. Jyoti Bajpai: Institutional financial interests for conducting research: Eli Lilly, MSD, Novartis, Roche, Paxman Coolers Ltd, Samsung Bioepis co. Ltd, Sun Pharma. Carlos H. Barrios: Receipt of grants/research supports: (to the institution) Nektar, Pfizer, Polyphor, Amgen, Daiichi Sankyo, Sanofi, Exelixis, Regeneron, Novartis, GSK, Janssen, OBI Pharma, Lilly, Seagen, Roche, BMS, MSD, Merck Serono, AstraZeneca, Novocure, Aveo Oncology, Takeda, TRIO, PharmaMar, Celgene, PPD, Syneos Health, Labcorp, ICON, IQVIA, Parexel, Nuvisan, PSI, Worldwide, Gilead Sciences, Bayer, Servier. Receipt of honoraria or consultation fees: Advisory Boards and Consulting: Boehringer-Ingelheim, GSK, Novartis, Pfizer, Roche/Genentech, Eisai, Bayer, MSD, AstraZeneca, Zodiac, Lilly, Sanofi, Daiichi. Stock shareholder: Ownership or stocks: Tummi, MEDSir. Jonas Bergh: Receipt of grants/research supports: Research grants from Amgen, AstraZeneca, Bayer, Merck, Pfizer, Roche & Sanofi-Aventis to Karolinska Institutet and/or University Hospital. No personal payments. Other support: Payment for a chapter in UpToDate on breast cancer prediction to Asklepios Medicin HB. Laura Biganzoli: Personal financial interests (Honoraria, consultancy or advisory role): Amgen, AstraZeneca, Boehringer-Ingelheim, Daiichi-Sankyo, Eisai, Exact Sciences, Gilead, Lilly, Menarini, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi, SeaGen. Institutional financial interests: Celgene, Genomic Health, Novartis. Travel grants: AstraZeneca, Daiichi-Sankyo. Fatima Cardoso: Receipt of honoraria or consultation fees: Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi-Sankyo, Eisai, GE Oncology, Genentech, Gilead, GlaxoSmithKline, Iqvia, Macrogenics, Medscape, Merck-Sharp, Merus BV, Mylan, Mundipharma, Novartis, Pfizer, Pierre-Fabre, prIME Oncology, Roche, Sanofi, Samsung Bioepis, Seagen, Teva, Touchime. Maria-Joao Cardoso: Receipt of honoraria or consultation fees: AstraZeneca, Merck-Sharp, Novartis and Roche. Lisa A. Carey: Other support: Research funding (institution): NanoString Technologies, Seagen, Veracyte, AstraZeneca. Uncompensated relationships: Lilly, Seagen, Novartis, Genentech/Roche, GlaxoSmithKline. Mariana Chavez-MacGregor: Receipt of grants/research supports: BCRF, Susan G Komen. Receipt of honoraria or consultation fees: Astra Zeneca, Pfizer, Lilly, Roche, Merck. Javier Cortés: Receipt of grants/research supports: Roche, Celgene, Cellestia, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Merck Sharp&Dohme, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics, Expres2ion Biotechnologies. Receipt of honoraria or consultation fees: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp&Dohme, Daiichi Sankyo, Astrazeneca. Stock shareholder: MedSIR, Nektar Pharmaceuticals, Leuko (relative). Other support: Research funding to the Institution: Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F.Hoffman-La Roche, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma C, Queen Mary University of London. Travel, accommodation, expenses: Roche, Novartis, Eisai, pfizer, Daiichi Sankyo, Astrazeneca, Gilead. Patents: Pharmaceutical Combinations of a Pi3k Inhibitor and A Microtubule Destabilizing Agent. Javier Cortés Castán, Alejandro Piris Giménez, Violeta Serra Elizalde. WO 2014/199294 A. ISSUED. Her2 as a predictor of response to dual HER2 blockade in the absence of cytotoxic therapy. Aleix Prat, Antonio Llombart, Javier Cortés.US 2019/0338368 A1. LICENSED. Giuseppe Curigliano: Receipt of grants/research supports: Merck. Receipt of honoraria or consultation fees: Merck, Lilly, Pfizer, Daichi Sankyo, Seagen, Novartis, Roche, Astra Zeneca, Ellipsis. Participation in a sponsored speakers' bureau: Seagen, Novartis, Lilly, Pfizer, Daichii Sankyo. Rebecca A. Dent: Receipt of grants/research supports: AstraZeneca, Roche. Receipt of honoraria or consultation fees: AstraZeneca, DKSH, Eisai, Merck, Novartis, Pfizer, Roche. Nagi S. El Saghir: Receipt of honoraria or consultation fees: Roche, Novartis, Lilly. Alexandru Eniu: Receipt of honoraria or consultation fees: Astra Zeneca, Daiichi Sankyo, Gilead, Janssen, MSD, Novartis, SeaGen. Receipt of grants/research supports: AstraZeneca. Full or part-time employment: European School of Oncology (ESO). Lesley Fallowfield: Receipt of grants/research supports: Novartis, Bristol-Myers Squibb, Lilly. Receipt of honoraria or consultation fees: Voluntis, Genomic Health, NanoString Technologies, Novartis, Pfizer, MSD, Novartis, Abbvie, Clovis Oncology, Puma Biotechnology, AstraZeneca, Takeda, Genomic Health/Exact Sciences, Lilly, Seagen, Roche. Sandra X. Franco Millan: Receipt of honoraria or consultation fees: Novartis, Pfizer, Eli Lilly. Participation in a sponsored speakers' bureau: Novartis, Pfizer, Eli Lilly. Karen Gelmon: Receipt of grants/research supports: Pfizer, AstraZeneca. Receipt of honoraria or consultation fees: Pfizer, Lilly, Novartis, AstraZeneca, Merck, Gilead, Seagen. Jenny Gilchrist: Receipt of honoraria or consultation fees: Eli-Lilly, AstraZeneca, Novartis, Pfizer, MSD, Gilead, Juniper Biologics. Joseph Gligorov: Receipt of grants/research supports: Eisai, Exact Science, Guardant, Roche Genentech. Receipt of honoraria or consultation fees: Astra Zeneca, Daiichi, Eisai, Evapharma, Exact Science, Gilead, Guardant Lilly, Merck, Novartis, Onxeo, Pfizer, Roche Genentech, Seattle Genetics. Participation in a sponsored speakers' bureau: Eisai, Eva Pharm, Novartis, Roche Genentech, Seattle Genetics. Other support (please specify): Institutional: Institut Universitaire de Cancérologie AP-HP Sorbonne Université; French breast cancer guidelines St Paul. Nadia Harbeck: Receipt of grants/research supports: all to institution. Receipt of honoraria or consultation fees: AstraZeneca, Daiichi-Sankyo, Gilead, Lilly, MSD, Novartis, PierreFabre, Pfizer, Roche, Sandoz, Seagen, Viatris, Zuelligpharma. Participation on a sponsored speakers' bureau: EPG Communication, MEDSCAPE, Springer. Stock shareholder: WSG minority ownership. Spouse/Partner: Consulting for WSG. Ranjit Kaur: Receipt of grants/research supports: Novartis, Roche, Pfizer, Astrazeneca. Receipt of honoraria or consultation fees: Novartis, Roche, Pfizer, Astrazeneca. Participation in a sponsored speakers' bureau: Novartis, Roche, Pfizer, Astrazeneca. Belinda Kiely: Receipt of honoraria or consultation fees: Speakers fees: Novartis, Eisai. Advisory boards: Roche, Gilead, Novartis. Other support (please specify): meeting registrations fees: Novartis, Pfizer, MSD. Sung-Bae Kim: Receipt of grants/research supports: Novartis, Sanofi-Aventis, and DongKook Pharm Co. Receipt of honoraria or consultation fees: Novartis, AstraZeneca, Lilly, Dae Hwa Pharmaceutical Co. Ltd, ISU Abxis, OBI pharma, Beigene and Daiichi-Sankyo. Stock shareholder: Genopeaks. Smruti Koppikar: Receipt of honoraria or consultation fees: Eli Lilly, Novartis, Cipla, Roche. Participation in a sponsored speakers' bureau: Eli Lilly, Novartis, Cipla, Roche. Marion Kuper-Hommel: Receipt of honoraria or consulting fees: Astra Zeneca. Ginny Mason: Participation in a sponsored speakers' bureau: Novartis. Volkmar Mueller: Receipt of grants/research supports: Institutional research support from Novartis, Roche, Seagen, Genentech, Astra Zeneca. Receipt of honoraria or consultation fees: Speaker honoraria: Astra Zeneca, Daiichi-Sankyo, Eisai, GSK, Pfizer, MSD, Medac, Novartis, Roche, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead, Pierre Fabre. Consultancy honoraria from Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, DaiichiSankyo, Eisai, Lilly, Sanofi, Seagen, Gilead, Stemline, ClinSol. Other support (please specify): Travel grants: Roche, Pfizer, Daiichi Sankyo, Gilead. Claire Myerson: Receipt of honoraria or consultation fees: Novartis Pharma. Silvia Neciosup: Receipt of grants/research supports: Roche, Pfizer. Participation in a sponsored speakers' bureau: Tecnofarma, AZ, Roche, Pfizer. Larry Norton: Receipt of honoraria or consultation fees: Blackrock QLS Advisors, Cold Spring Harbor Laboratory, UNC Breast Spore EAB Meeting, Codagenix Scientific Advisory Board Meeting, Martell Diagnostic Laboratories, Inc., Celgene, Agenus, Immix Biopharma, Inc. Shinji Ohno: Participation in a sponsored speakers' bureau: Chugai, Lilly, MSD, Nippon Kayaku. Shani Paluch-Shimon: Receipt of grants/research supports: Pfizer. Receipt of honoraria or consultation fees: Pfizer, Lily, Novartis, Astra Zeneca, Roche, MSD, Gilead, Rhenium/Exact Sciences, Stemline, Daichi Sankyo. Participation in a sponsored speakers' bureau: Pfizer, Lily, Novartis, Astra Zeneca, Roche, MSD, Gilead. Ann H. Partridge: Uptodate Royalties. Aleix Prat: Receipt of grants/research supports: Boehringer, Novartis, Roche, Nanostring, Sysmex Europa GmbH, Medica Scientia inno. Research, SL, Celgene, Astellas and Pzifer. Receipt of honoraria or consultation fees: Roche, Pfizer, Novartis, Amgen, BMS, Puma, Oncolytics Biotech, MSD, Guardan Health, Peptomyc and Lilly, Nanostring Technologies and Daiichi Sankyo. Other support: Clinical trials: Boehringer, Lilly, Roche, Novartis, Amgen and Daiichi Sankyo. Hope S. Rugo: Receipt of grants/research supports: Astellas Pharma Inc.; AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche AG/Genentech, Inc.; Gilead Sciences, Inc.; GlaxoSmithKline; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Pfizer; Pionyr Immunotherapeutics; Sermonix Pharmaceuticals Inc.; Taiho Oncology, Inc. and Veru Inc. Receipt of honoraria or consultation fees: Puma, NAPO, Blueprint, and Scorpion Therapeutics Daichi Sankyo. Elzbieta Senkus: Receipt of honoraria or consultation fees: AstraZeneca, Curio Science, Egis, Eli Lilly, Gilead, high5md, MSD, Novartis, Pfizer, Roche, Swixx. Other support: travel support: AstraZeneca, Egis, Gilead, Novartis, Roche. Contracted research: Amgen, AstraZeneca, Eli Lilly, Gilead, Novartis, OBI Pharma, Roche, Samsung, Seagen. Medical writing: AstraZeneca, Eli Lilly. Royalties: Springer. Sandra M. Swain: Receipt of grants/research supports: Kailos Genetics, Genentech/Roche. Receipt of honoraria or consultation fees: Athenex, AstraZeneca, Biotheranostics, Natera, Exact Sciences, Lilly, Merck, Genentech/Roche, Sanofi, Daiichi Sankyo, Molecular Templates, Napo Pharmaceuticals. Stock shareholder: SEAGEN. Other support: CO- PI of INAVO 122 Genentech/Roche with in-kind travel to investigator meetings, Travel related expenses in kind Sanofi and Daiichi Sankyo. Peter Vuylsteke: Receipt of grants/research supports: UICC grant. Receipt of honoraria or consultation fees: Roche, Novartis and MSD. Theresa Wiseman: Receipt of grants/research supports: Receiver of SPCC Pfizer grant. Binghe Xu: Receipt of grants/research supports: sponsored research to my institution from Roche, AstraZeneca and Pfizer. Receipt of honoraria or consultation fees: advisory or consultancy fees from Novartis and Roche. Participation in a sponsored speakers' bureau: speakers’ bureau fees from AstraZeneca, Pfizer, Roche, Eisai. Elizabeth Bergsten-Nordström, Alberto Costa, Runcie C. W. Chidebe, Prudence A. Francis, Xichun Hu, Renate Haidinger, Leonor Matos, Shirley A. Mertz, Birgitte V. Offersen, Olivia Pagani, Eva Schumacher-Wulf, Daniel A. Vorobiof, Frédéric E. Lecouvet, and Eric P. Winer reported no significant relationships. William J. Gradishar, George W. Sledge and Christoph Thomssen have not submitted a disclosure of interests’ form., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The Swiss Group for Clinical Cancer Research (SAKK) conducted the SAKK 35/03 randomized trial (NCT00227695) to investigate different rituximab monotherapy schedules in patients with follicular lymphoma (FL). Here, we report their long-term treatment outcome. Two-hundred and seventy FL patients were treated with 4 weekly doses of rituximab monotherapy (375 mg/m2); 165 of them, achieving at least a partial response, were randomly assigned to maintenance rituximab (375 mg/m2 every 2 months) on a short-term (4 administrations; n = 82) or a long-term (up to a maximum of 5 years; n = 83) schedule. The primary end point was event-free survival (EFS). At a median follow-up period of 10 years, median EFS was 3.4 years (95% confidence interval [CI], 2.1-5.5) in the short-term arm and 5.3 years (95% CI, 3.5-7.5) in the long-term arm. Using the prespecified log-rank test, this difference is not statistically significant (P = .39). There also was not a statistically significant difference in progression-free survival or overall survival (OS). Median OS was 11.0 years (95% CI, 11.0-NA) in the short-term arm and was not reached in the long-term arm (P = .80). The incidence of second cancers was similar in the 2 arms (9 patients after short-term maintenance and 10 patients after long-term maintenance). No major late toxicities emerged. No significant benefit of prolonged maintenance became evident with longer follow-up. Notably, in symptomatic patients in need of immediate treatment, the 10-year OS rate was 83% (95% CI, 73-89%). These findings indicate that single-agent rituximab may be a valid first-line option for symptomatic patients with advanced FL., (© 2020 by The American Society of Hematology.)

Competing Interests: Disclosure MSA reports receipt of consultation fees from Amgen, BMS, Celgene, Clinigen, Eisai, Genomic Health, GSK, Helsinn, Hospira, JnJ, Novartis, Merck, Merck Serono, Mundipharma, Pfizer, Pierre Fabre, Roche, Sandoz, Tesaro, Tevam Vifor, G1 Therapeutics and Lilly; receipt of honoraria for symposia lectures from Amgen, Bayer, Schering, Cephalon, Chugai, Eisai, Genomic Health, GSK, Helsinn, Hospira, Ipsen, JnJ Ortho Biotech, Kyowa Hakko Kirin, Merck, Merck Serono, Mundipharma, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz, Sanofi, Tesaro, Taiho, Tevam Vifor, G1 Therapeutics and Lilly. CHB reports receipt of honoraria or consultation fees from Boehringer Ingelheim, GSK, Novartis, Pfizer, Roche/Genentech, Eisai, MSD, AstraZeneca and Bayer; receipt of grants/research support to the institution from AbbVie, Amgen, Astellas Pharma, AstraZeneca, BMS, Celgene, Covance, Lilly, Medivation, Merck Serono, MSD, Novartis, Pfizer, PharmaMar and Roche/Genentech. JB reports receipt of grants/research support grants to Karolinska Institute and University Hospital from Amgen, AstraZeneca, Bayer, Merck, Pfizer, Roche, Sanofi-Aventis; no personal payments; payment from UpToDate to Asklepios Medicine HB for a chapter on breast cancer prediction. LB reports receipt of grants/research support from Celgene, Genomic Health and Novartis; receipt of honoraria or consultation fees from AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Genomic Health, Ipsen, Lilly, Novartis, Pfizer, Pierre Fabre and Roche. FC reports receipt of honoraria or consultation fees from Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, GE Oncology, Genentech, GSK, MacroGenics, Medscape, MSD, Merus BV, Mylan, Mundipharma, Novartis, Pfizer, Pierre Fabre, prIME Oncology, Roche, Sanofi, Seattle Genetics and Teva. JC reports acting as a consultant/advisor for Roche, Celgene, Cellestia, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Servier, MSD, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim and Kyowa Kirin; received honoraria from Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, MSD and Daiichi Sankyo; received research funding to the institution from Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer Healthcare, Eisai, F. Hoffmann-La Roche, Guardant Health, MSD, Pfizer, PIQUR Therapeutics, Puma C and Queen Mary University of London; holds stock, patents and intellectual property for MEDSIR; received travel, accommodation and expenses from Roche, Novartis, Eisai, Pfizer and Daiichi Sankyo. GC reports receipt of honoraria or consultation fees from Roche, Pfizer, Lilly, Novartis and SeaGen; participation in a sponsored speakers' bureau for SeaGen, Pfizer, Lilly and Novartis. NSES reports receipt of grants/research support to institution from Novartis; receipt of honoraria or consultation fees from Novartis, Roche, Pfizer, Lilly and AstraZeneca. ME reports acting in an advisory role for Novartis and Roche. AE reports receipt of grants/research support from AstraZeneca, Roche, Celltrion, Pfizer and Novartis. LF reports receipt of grants/research support from BMS, GSK, Myriad and Novartis; receipt of honoraria or consultation fees from BMS, AstraZeneca, Teva, Novartis, Eisai, Takeda, Pfizer, Lilly, Genomic Health and Myriad. PAF reports receipt of honoraria or consultation fees from AstraZeneca and Novartis; travel for lecture for Pfizer and Ipsen. KG reports receipt of grants/research support from AstraZeneca, Pfizer and BMS; receipt of honoraria or consultation fees from Pfizer, AstraZeneca, Novartis, Nanostring, Merck, Mylan, Genomic Health, Roche and BMS. JG reports receipt of grants/research support from Amgen, Eisai, Genomic Health, Novartis, Pfizer and Roche/Genentech; receipt of honoraria or consultation fees from Daiichi, Eisai, Genomic Health, Ipsen, MacroGenics, MSD, Mylan, Novartis, Onxeo, Pfizer and Roche/Genentech; participation in a sponsored speakers' bureau for Eisai, Genomic Health, Ipsen, Novartis, Pfizer and Roche/Genentech. NH reports receipt of honoraria or consultation fees from Amgen, AstraZeneca, Celgene, Daiichi Sakyo, Lilly, MSD, Novartis, Odonate, Pfizer, Roche, Sandoz/Hexal and Seattle Genetics. RK reports receipt of grants/research support from Pfizer Malaysia. BEK reports receipt of grants/research support to institution from Roche; receipt of honoraria for advisory boards and educational presentations as well as travel and meeting expenses from Roche; receipt of honoraria for advisory boards and educational presentations from Novartis. SBK reports receipt of grants/research support to institution from Novartis, Sanofi-Aventis, Kyowa Kirin Inc. and DongKook Pharm Co.; receipt of consultancy fees from Novartis, AstraZeneca, Lilly, Enzychem, Daehwa Pharmaceutical Co. Ltd, ISU ABXIS and Daiichi Sankyo. NUL reports receipt of grants/research support from Genentech and Seattle Genetics; receipt of honoraria or consultation fees from Seattle Genetics, Daiichi Sankyo and Puma. SAM reports receipt of honoraria from Pfizer and Lilly; SN reports receipt of grants/research support from Roche, Pfizer, BMS and Novartis; participation in a sponsored speakers' bureau for Roche, Pfizer, BMS, Merck and Novartis. LN reports receipt of honoraria from Sermonix Oncology Ad Board, Prime Oncology, Sarah Lawrence Lecture, Context advisory board, Oncology Pioneers Science Lecture Series, BCRF programmatic review meeting and CSHL external advisory board meeting. SO reports receipt of grants/research support from Chugai, Eisai, Taiho, Daiichi Sankyo; participation in a sponsored speakers' bureau for Chugai, AstraZeneca, Eisai, Taiho, Pfizer and Lilly. OP reports participation in a sponsored speakers' bureau for Takeda, Roche, Pfizer, Novartis and Lilly. SPS has participated in a speakers' bureau and received honoraria from Roche, AstraZeneca, Novartis, Pfizer, Nanostring and Teva; reports consultancy for Roche, AstraZeneca, Novartis and Pfizer. FPL reports receipt of grants/research support from Roche; receipt of honoraria or consultation fees from Roche, Puma, Pierre Fabre and AstraZeneca. AP reports personal financial interests and lecture fees for Roche, Pfizer, Novartis, Amgen, BMS and Daiichi Sankyo; participation in an advisory role/consultancy for Roche, Pfizer, Novartis, Amgen, BMS, Puma and Oncolytics Biotech; institutional financial interests include contracted research for Novartis, Nanostring, Roche and Boehringer; lecture fees from Nanostring technologies; clinical trials for Novartis, Roche, Boehringer, Daiichi Sankyo, Pfizer, Lilly and Amgen. HSR reports receipt of grants/research support from Pfizer, Merck, Novartis, Lilly, Genentech, OBI, Odonate, Daiichi Sankyo, Eisai, Seattle Genetics, MacroGenics and Immunomedics. ES reports receipt of honoraria or consultation fees from Amgen, AstraZeneca, Clinigen, Egis, Eli Lilly, Genomic Health, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz and TLC Biopharmaceuticals; travel support from Amgen, AstraZeneca, Egis, Novartis, Pfizer and Roche; contracted research for Amgen, AstraZeneca, Boehringer, Eli Lilly, Merck, Novartis, Pfizer, Roche and Samsung; holds stock in Eli Lilly. EPW reports receipt of grants/research support from Merck and Genentech/Roche; receipt of honoraria or consultation fees from Carrick Therapeutics, Genentech/Roche, Genomic Health, GSK, Jounce, Leap, Lilly, Merck and Seattle Genetics; research fees to institute from Genentech/Roche and Merck; participation in a scientific advisory board for Leap. BX reports receipt of advisory fees from Novartis and Roche; fees for serving on a speakers' bureau from AstraZeneca, Pfizer, Roche and Eisai. FA, FB, BK, FEL, GWS, CT and TW have not reported any potential conflict of interest. GSB, MJC, LAC, AC, RH, XH, BVO and DAV have declared no significant conflict of interest.

Aim: We investigated the prognostic potential of pretherapy measurement of the neutrophil/lymphocyte ratio (NLR) in patients (n = 56) with non-small-cell lung cancer deemed suitable for treatment with nivolumab., Materials & Methods: This was a multicenter, noninterventional, retrospective data analysis, involving five oncology centers., Results: Patients with prenivolumab NLR values of <5 and ≥5 had respective median overall survival (OS) values of 14.5 and 7.02 months (p = 0.0026). Patients with ≤2 and >2 metastatic sites had median OS values of 11.4 and 6.1 months, respectively (p = 0.0174). A Cox multiple regression model revealed baseline NLR ≥5 as the only variable significantly associated with decreased OS (p < 0.0447)., Conclusion: Pretreatment elevated NLR values are associated with poor outcomes in patients with recurrent metastatic non-small-cell lung cancer treated with nivolumab., Competing Interests: Financial & competing interests disclosure BL Rapoport reports personal fees from Merck and Co, grants and personal fees from BMS, grants and personal fees from Roche South Africa, personal fees from AstraZeneca, during the conduct of the study. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. The final manuscript was supported in its entirety by the investigators. No writing assistance was utilized in the production of this manuscript., (© 2020 Rapoport BL.)

Over the past few decades, the systemic therapy of breast cancer (early and advanced) has changed considerably. For the past 40-50 years, and since the discovery and further therapeutic use of tamoxifen, a selective estrogen receptor modulator, breast cancer treatment has become the model for the development and success of tailored medical treatment. Much still needs to be done in improving outcomes for all patients with breast cancer, and especially for those who have advanced breast cancer, a challenging area for medical oncologists. Ongoing international clinical trials are currently evaluating new therapeutic approaches and identifying specific biological subsets that could determine a patient's ability to respond to particular chemotherapeutic drugs., Competing Interests: The author declares that he has no competing interests. No competing interests were disclosed. No competing interests were disclosed.

Purpose: The primary objective of this study was to evaluate 1- and 2-year survival rates and durable remissions in pretreated patients with advanced (unresectable or metastatic) malignant melanoma treated with ipilimumab in a South African expanded-access program (SA-EAP)., Patients and Methods: This multicenter, retrospective study obtained data from pretreated patients with advanced malignant melanoma who were eligible for the ipilimumab SA-EAP. Ipilimumab was administered at a dose of 3 mg/kg intravenously every 3 weeks for four cycles to adults with advanced melanoma for whom at least one line of treatment for metastatic disease had failed. Data from the medical records of 108 patients treated within the SA-EAP were collected and statistically analyzed to determine overall (OS) and progression-free survival (PFS) at 1 and 2 years., Results: In the population of 108 patients, a median OS of 8.98 months (95% CI, 7.47 to 10.79 months) was observed. One-year OS was 36% (95% CI, 26% to 45%), and 2-year survival was observed as 20% (95% CI, 12% to 27%). The median survival without progression (ie, PFS) was 3.44 months (95% CI, 2.98 to 4.16 months), and 1- and 2-year PFS were 22% (95% CI, 14% to 29%) and 14% (95% CI, 8% to 21%), respectively. The longest recorded survival was 3.4 years. No independent prognostic variables were identified to predict for OS by multivariate Cox proportional hazards model., Conclusion: In this multicenter South African setting, ipilimumab at a dose of 3 mg/kg was an effective treatment with long-term OS in a subset of patients with pretreated advanced malignant melanoma., Competing Interests: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc. Bernardo L. RapoportHonoraria: Tesaro, Merck, Bristol-Myers Squibb Consulting or Advisory Role: Tesaro, Merck, Bristol-Myers Squibb Speakers’ Bureau: Tesaro, Merck, Bristol-Myers Squibb Research Funding: Tesaro, Merck, Bristol-Myers Squibb Travel, Accommodations, Expenses: Tesaro, Merck, Bristol-Myers SquibbDaniel A. VorobiofConsulting or Advisory Role: Amgen, Roche, Bristol-Myers SquibbLydia M. DreostiHonoraria: Roche, Janssen Pharmaceuticals Consulting or Advisory Role: Roche, Janssen Pharmaceuticals, Novartis Speakers’ Bureau: Janssen Pharmaceuticals Travel, Accommodations, Expenses: Roche, Janssen Pharmaceuticals, Merck SeronoAdam NosworthySpeakers’ Bureau: Key Oncologics Travel, Accommodations, Expenses: Bristol-Myers Squibb, Janssen OncologyGeorgina McAdamNo relationship to discloseJohan P. JordaanSpeakers’ Bureau: Merck Serono Research Funding: Roche, PAREXEL International, Ipsen, Quintiles, Novartis Travel, Accommodations, Expenses: RocheHelen Miller-JansönConsulting or Advisory Role: HEXOR (Inst) Research Funding: HEXOR (Inst)Margreet de NeckerConsulting or Advisory Role: HEXOR (Inst) Research Funding: HEXOR (Inst)Janetta C. de BeerConsulting or Advisory Role: HEXOR (Inst) Research Funding: HEXOR (Inst)Hennie DuvenhageEmployment: Bristol-Myers Squibb Research Funding: Bristol-Myers Squibb

Purpose: Rituximab maintenance therapy has been shown to improve progression-free survival in patients with follicular lymphoma; however, the optimal duration of maintenance treatment remains unknown., Patients and Methods: Two hundred seventy patients with untreated, relapsed, stable, or chemotherapy-resistant follicular lymphoma were treated with four doses of rituximab monotherapy in weekly intervals (375 mg/m(2)). Patients achieving at least a partial response were randomly assigned to receive maintenance therapy with one infusion of rituximab every 2 months, either on a short-term schedule (four administrations) or a long-term schedule (maximum of 5 years or until disease progression or unacceptable toxicity). The primary end point was event-free survival (EFS). Progression-free survival, overall survival (OS), and toxicity were secondary end points. Comparisons between the two arms were performed using the log-rank test for survival end points., Results: One hundred sixty-five patients were randomly assigned to the short-term (n = 82) or long-term (n = 83) maintenance arms. Because of the low event rate, the final analysis was performed after 95 events had occurred, which was before the targeted event number of 99 had been reached. At a median follow-up period of 6.4 years, the median EFS was 3.4 years (95% CI, 2.1 to 5.3) in the short-term arm and 5.3 years (95% CI, 3.5 to not available) in the long-term arm (P = .14). Patients in the long-term arm experienced more adverse effects than did those in the short-term arm, with 76% v 50% of patients with at least one adverse event (P < .001), five versus one patient with grade 3 and 4 infections, and three versus zero patients discontinuing treatment because of unacceptable toxicity, respectively. There was no difference in OS between the two groups., Conclusion: Long-term rituximab maintenance therapy does not improve EFS, which was the primary end point of this trial, or OS, and was associated with increased toxicity., Competing Interests: Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article., (© 2015 by American Society of Clinical Oncology.)

Introduction: Two previous cases of the development of Dupuytren's contractures were reported in association with BRAF inhibitor treatment for BRAF V600E mutation-positive metastatic melanoma and metastatic papillary thyroid carcinoma. We reported on a third case with a slower onset of presentation., Case Presentation: A 66-year-old white man was diagnosed with a BRAF V600E mutated metastatic cutaneous melanoma. He was commenced on oral vemurafenib 960 mg twice daily. A marked response was achieved for his metastatic disease. He noticed a change of his hair characteristics and a feeling of "lumps" in both palms by 6 months. By 9 months, classical Dupuytren's contracture was apparent., Conclusions: Dupuytren's contracture is not a known side effect of BRAF inhibitor treatment. The timeline for the development of Dupuytren's contracture on BRAF inhibitor treatment is not well defined. Although the etiology of Dupuytren's contracture is unknown, an increase in tumor necrosis factor has been demonstrated to be a possible mechanism. BRAF inhibition has been shown to increase immune reaction in the tumor microenvironment and is associated with high serum tumor necrosis factor level. We propose that an increased level of tumor necrosis factor associated with BRAF inhibition may increase the risk of the development of Dupuytren's contractures.

Opinion Statement: Bisphosphonates have emerged as an important tool in the supportive care of women with early breast cancer. Whereas traditionally, these drugs have been part of the treatment of osseous metastasis, the key role of bisphosphonates in preserving bone health in patients with early breast cancer cannot be overemphasised. Currently the most established use of bisphosphonates in early breast cancer patients is in women receiving hormonal blockade, mostly aromatase inhibitors (AI), with concomitant osteopenia. To that end, it is recommended that every woman undergo a Dual Energy X-Ray absorptiometry (DEXA) scan before commencement of an AI and annually during the treatment duration. In addition, unless contraindicated, all women should receive calcium and Vitamin D supplementation. The use of bisphosphonates as part of the adjuvant therapy strategy, regardless of baseline bone density condition, has produced thought-provoking results, although this is not yet considered standard clinical practise.

Purpose: To determine if concomitant administration of docetaxel plus zosuquidar.3HC1 can prolong progression-free survival in patients with metastatic breast cancer., Methods: A randomized, double-blind, multicenter, placebo-controlled clinical trial comparing docetaxel plus 500 mg zosuquidar.3HCl (DZ) with docetaxel plus placebo (DP)., Results: A total of 170 patients were enrolled and randomly assigned to treatment. The median age was 53 years (range, 31-74 years). 81.7% of patients had prior chemotherapy in the adjuvant setting and 18.3% in the neoadjuvant setting. The median progression-free survival time was statistically different between groups [7.2 months (DZ) vs. 8.3 months (DP)]. Once the stratification factor relative to progression following prior chemotherapy was considered, no significant treatment difference existed., Conclusion: The combination of zosuquidar.3HCl plus docetaxel is safe. The analysis of efficacy data is complex, but it can be concluded that there is no difference in progression-free survival, overall survival, or response rate in the study as a whole.

Objective: This phase II study assessed the activity and safety of pegylated liposomal doxorubicin (PLD) plus carboplatin in relapsed ovarian cancer (ROC)., Method: Forty women with platinum-sensitive and partially platinum-sensitive ROC were treated with PLD 50 mg/m2 plus carboplatin area under the curve 5 every 28 days in this South African multicenter study. All patients who completed 3 cycles of chemotherapy were evaluated for response. Primary outcome was response in the intent-to-treat population., Results: Complete response was 35%, and partial response was 32.5% (overall response, 67.5%). Median time-to-progression was 11.9 months, and median survival was 30.0 months. Overall response was higher in platinum-sensitive (81%) versus partially platinum-sensitive patients (53%), as were median duration of response, median time-to-progression, and median survival. Treatment was well tolerated, with no grade 4 nonhematologic toxicities. Grade 3/4 hematologic toxicities included leukopenia (58%), neutropenia (55%), and thrombocytopenia (43%)., Conclusion: Pegylated liposomal doxorubicin plus carboplatin is well tolerated and active in the treatment of platinum-sensitive and partially platinum-sensitive ROC.

Malignant pleural mesothelioma (MPM) is a disease usually unaffected by current therapeutic strategies, but for the majority of patients, the use of systemic chemotherapeutic drugs remains the only therapeutic option available. During the past 15-20 years, many phase II and a few phase III clinical trials have studied a large variety of drugs such as anthracyclines, alkylating agents, platinum compounds, taxanes, vinka alkaloids, and antifolates as single agents and in combination, with the aim to increase responses and survival. The combination of pemetrexed and cisplatin tested in the largest phase III randomized trial of malignant pleural mesothelioma ever conducted has become the current standard of care. New targeted therapeutic approaches with a variety of anti-growth factor drugs are currently undergoing investigation worldwide.

Asbestos has been used by man since 4000 before the Christian era (BCE) in many different parts of the world and for a wide range of functions. Blue asbestos (crocidolite) was first discovered in South Africa in 1805 and within a few years was being mined there extensively. Mining reached its peak in 1977 with >380,000 tons being exported and 20,000 miners employed in the industry. South Africa also has large deposits of white asbestos (chrysotile) and brown asbestos (amosite) both of which have been mined extensively. At the turn of the 20th century, it was noted that those working with asbestos suffered lung disease and in 1960, the link between asbestosis and mesothelioma was established in the Kimberley area of South Africa. Further studies in the 1970s and 1980s showed an alarming incidence of mesothelioma based on pathology reports. The majority of the reported mesothelioma cases result from exposure to asbestos in its many uses in secondary industry although incidence of the condition among miners is also significant. A high proportion of mesothelioma in patients in South Africa is attributed to environmental origin with a high incidence of women and children affected.

The aim of this multicentric phase II study was to investigate the efficacy and toxicity of a combination of chemotherapy containing paclitaxel (Taxol) and a novel compound, a liposomal encapsulated doxorubicin (Caelyx), as first line therapy for patients with metastatic breast cancer. Thirty-four patients with advanced breast cancer were treated with a combination of paclitaxel 175 mg/m2 and liposomal doxorubicin 30 mg/m2, every 3 weeks. The combination chemotherapy was effective in 73% of the patients (ITT) (95% CI 55-86%) (7 complete and 18 partial responses). Grade 3/4 toxicities were documented in a small number of patients. Two toxic deaths (6%) were documented, one a hepatorenal failure and another a febrile neutropenia. One patient experienced pulmonary embolism but continued on treatment after appropriate therapy. The combination of paclitaxel and liposomal encapsulated doxorubicin induces a high and durable response rate with a moderate toxicity profile., (Copyright 2004 Elsevier Ltd.)

During the past 2 decades there have been chemotherapeutic advances in the management of patients with advanced epithelial ovarian cancer. Nevertheless, new drug combinations aimed at increasing response and survival and decreasing toxicities are under investigation. The aim of this phase II study is to determine the feasibility, efficacy and toxicity of docetaxel at a dose of 75 mg/m2 in combination with Carboplatin at an area under the curve (AUC) of 6, as first line treatment in patients with advanced ovarian cancer. 37 patients with stage III-IV epithelial ovarian cancer were entered, and are currently evaluable for response and toxicity. Treatment was well tolerated. The most common grade III and IV toxicities were leukopenia and neutropenia. The incidence of febrile neutropenia was 16.2%. Grade II and III sensory peripheral neuropathy occurred in 8.1% of patients. Peripheral neuropathy resolved in two patients and persisted for more than 10 months in one patient. An overall clinical response of 89% was documented (95% CI 74.5% to 96.9%). Carboplatin and docetaxel administered according to our protocol is an effective alternative to other existing platinum-taxane based combinations. This treatment is associated with low incidence of sensory peripheral neuropathy, which is generally associated with better patient compliance and quality of life.

We report a rare case of primary osteosarcoma of the breast in a postmenopausal patient without any association to either trauma or an underlying tumor. Clinical, radiographic, and histologic illustrations as well as a review of the literature are presented.

Fourteen patients with metastatic malignant melanoma that had failed to respond to standard dacarbazine-based chemotherapy treatment were entered into a phase II study of pegylated liposomal doxorubicin (Caelyx) given as a single intravenous injection at a dose of 50 mg/m(2) at 28 day intervals. No objective responses were documented. Treatment was well tolerated. We conclude that pegylated liposomal doxorubicin does not demonstrate sufficient activity in metastatic melanoma to warrant further investigation in this setting.

Current cytotoxic therapy has been of limited benefit to patients with malignant pleural mesothelioma. Single agent chemotherapy has been extensively evaluated in small series of phase II clinical trials, with disappointing responses. Docetaxel, an effective taxane in the treatment of advanced breast cancer and non-small-cell lung cancer, was administered intravenously at a dose of 100 mg/m2 every 3 weeks to 30 chemotherapy naive patients with malignant pleural mesothelioma in a prospective multi-institutional phase II clinical trial. An objective response rate (partial responses) of 10% was documented. Additionally, 21% of the patients had minor responses (intention-to-treat analysis). Three patients died within 2 weeks post-first cycle of therapy, although only one patient's death was directly attributed to the investigational drug, whilst in the majority of the patients, manageable and treatable toxicities were encountered. In this phase II clinical trial, docetaxel proved to be mildly effective in the treatment of patients with malignant pleural mesothelioma.

Cancer in South Africa is an emerging health problem, with breast cancer being one of the leading cancers in women, following similar worldwide statistics. Lifetime risks of developing breast cancer vary from a low of one in 81 in African women (similar to Japan) to a high of one in 13 among white women, similar to rates in Western countries. Age and stage at diagnosis vary considerably between the different races and populations (urban v rural) living in South Africa. Many different determinants (socioeconomic, cultural, geographic accessibility to medical centers with oncologic services, availability of traditional healers, and so on) affect patients with breast cancer (mainly rural black women) in their decisions to obtain early medical help as well as to refrain from the proposed therapeutic methods (surgery, radiotherapy, and chemotherapy). A brief overview of breast cancer in South Africa with special reference to some of the above determinants is presented.

Background: This study provides a direct randomized comparison of a new-generation, non-steroidal aromatase inhibitor, anastrozole (Arimidex), with a steroidal aromatase inhibitor (formestane) with respect to oestrogen (oestradiol, oestrone, and oestrone sulphate) suppression and tolerability., Patients and Methods: Sixty postmenopausal women with advanced breast cancer were randomized to receive either anastrozole 1 mg once daily orally (n = 29), or formestane 250 mg once every two weeks by intramuscular injection (n = 31). Treatment was continued until progression of disease or withdrawal from the study. The primary endpoints of this study were oestradiol suppression and tolerability. The secondary endpoints included oestrone and oestrone sulphate suppression. All laboratory analyses were conducted 'blind' of the randomized drug treatment., Results: Anastrozole produced a greater and more consistent suppression of oestradiol levels compared with formestane. Based on two- and four-week measurements, the mean fall from baseline (pre-dose) in oestradiol level was 79% and 58% in the anastrozole and formestane groups, respectively (P = 0.0001). After four weeks of treatment, oestrone and oestrone sulphate levels were also suppressed to a greater extent by anastrozole compared with formestane (oestrone: 85% versus 67%, respectively, P = 0.0043; oestrone sulphate: 92% versus 67%, respectively, P = 0.0007). No statistical differences were seen between the two drugs in the incidence of adverse events., Conclusions: Anastrozole provides a more consistent and significantly more effective suppression of oestradiol compared with formestane. Similar results were observed for oestrone and oestrone sulphate. The clinical significance of these differences in total oestrogen suppression remains to be established.

Purpose: This multicentre phase II trial was conducted in South Africa to evaluate the activity of a combination of vinorelbine, administered in a new schedule, and cisplatin, in chemonaive patients with advanced non-small-cell lung cancer (NSCLC)., Patients and Methods: Between September 1995 and December 1996, 35 patients were enrolled. All patients had at least one bidimensionally measurable lesion. Vinorelbine was administered intravenously on day 1 and day 8 at a dose of 30 mg/m2 and cisplatin was administered intravenously on day 1 at a dose of 100 mg/m2. The chemotherapy cycle was repeated every three weeks., Results: Of 35 evaluable patients, 14 (40%) achieved a response (one complete response and 13 partial responses). The median time to progression was 6.4 months (range 12-572 days) and the median survival was 15.7 months (range 12-882+ days). One-year survival was 56%. Toxicity was manageable and consisted of nausea and vomiting (grade 3 in 45% of patients) and grade 3-4 neutropenia seen in 13 patients with three patients experiencing grade 3 infection. Other side-effects were mild, including constipation grade 3 in 9.1%. A total of 153 courses were administered with patients receiving a median dose intensity of 81.7% for vinorelbine, while that of cisplatin was 74.1%., Conclusion: The combination of vinorelbine and cisplatin demonstrated substantial activity in terms of objective response and survival with manageable side-effects in patients with advanced NSCLC. These findings confirm the data from previous randomised studies. Further studies are ongoing in order to evaluate the efficacy of this combination in the neoadjuvant and adjuvant setting.

The relative efficacy and tolerability of the aromatase inhibitors anastrozole (Arimidex) and formestane are assessed in a direct comparative trial in postmenopausal women with advanced breast cancer. Final results are available and reported here only for oestradiol suppression. Patients were randomised to receive either oral anastrozole, 1 mg once daily, or formestane, 250 mg every 2 weeks intramuscularly. In the anastrozole group, mean serum oestradiol levels fell from 32.1 pmol/l at baseline to 6.5 pmol/l at week 1, and similar levels of suppression were maintained over the next 3 weeks. In the formestane group, mean serum oestradiol levels fell from 31.0 pmol/l at baseline to 9.5 pmol/l at the week 1 assessment. In this group, serum oestradiol levels tended to rise by the 2- and 4-week measurements, i.e. immediately before the next injection was due. Based on the 2- and 4-week measurements, the mean falls in oestradiol levels were 79 and 58% in the anastrozole and formestane groups, respectively (p = 0.0001). More effective and consistent suppression of oestradiol was achieved with anastrozole at the therapeutic dose of 1 mg once daily, orally, than with formestane at the standard dose of 250 mg every 2 weeks, intramuscularly.

60 patients were entered into a randomised study comparing vindesine (3 mg/m2/week) plus interferon-alpha 2b (6 U/m2 3 times per week) to vindesine alone or to interferon alone for the treatment of metastatic malignant melanoma. Patients receiving the combination therapy arm (schedule A; vindesine plus interferon-alpha 2b) showed a complete and partial response rate of 8/20 (40%) which was significantly higher (P < 0.05) than that achieved with either single-agent treatment schedule. In addition, patients receiving the combined treatment schedule had a significantly prolonged survival (median 19 months) when compared to a median of 10 months for interferon alone and 5 months for vindesine alone. The combination was generally well tolerated with only additive toxicity. It is concluded that combination treatment regimens utilising interferons together with chemotherapeutic agents deserve further study in the treatment of metastatic malignant melanoma.

Thirty-five patients with advanced prostatic cancer were entered in a trial of nasally administered gonadotropin-releasing hormone analogue agonist (GnRHA) buserelin. Four patients were unevaluable for response and toxicity. Twenty-five patients responded to treatment, two with complete remissions, 12 with partial remissions, and 11 who improved. The median baseline value for testosterone was 14.4 nmol/L. After 1 week of treatment, the median value was 10.8 nmol/L, while after 1 month the median value had decreased to 1.1 nmol/L (normal, 10.0 to 34.7). It is concluded that intranasal buserelin is an effective, simple, and safe method to achieve androgen deprivation in the treatment of advanced prostate cancer and is an alternative to orchiectomy and more acceptable than daily subcutaneous injections.

A prospective study of 120 patients with cancer was carried out to evaluate the effects of potentially cardiotoxic anticancer drugs using radionuclide cardiovascular studies. Five groups were studied: 7 patients received 4'-demethoxydaunorubicin, 23 4'-deoxydoxorubicin, 34 4'-epidoxorubicin, 49 mitoxantrone and 7 4'-(9-acridinylamino)-methan-sulphon-m-anisidide (amsa). Two patients receiving 4'-demethoxydaunorubicin, 7 on 4'-deoxydoxorubicin, 11 on 4'-epidoxorubicin, 21 on mitoxantrone and 3 on amsa had falls of greater than or equal to 10% in their left ventricular ejection fraction. Using data from this study, the recommended guidelines are set out.

A 60-year-old man with bilateral lung metastases from breast cancer was treated with the gonadotropin-releasing hormone analogue, buserelin, given as an intranasal spray. Androgen deprivation and complete remission of lung metastases were achieved with minimal side effects. Androgen deprivation by means of nasally administered buserelin offers an easy and efficient alternate approach in the treatment of metastatic male breast cancer.

Nineteen patients with histologically confirmed malignant mesothelioma were treated with m-AMSA at the University of Pretoria. All patients had evaluable disease and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-3. m-AMSA 120 mg/m2 was given IV every 3 weeks. Hematopoietic suppression was the major side-effect. Eleven patients developed leukopenia. There was one partial response (16 weeks), and a no change status was documented in 12 patients (median duration of 20 weeks). The median survival time of patients was 27 weeks from entry on study. Radionuclide ventricular ejection fraction tests were performed to evaluate cardiac function.

From 1965 to 1985, 262 patients with malignant pleural mesothelioma were treated with cytostatics only; radiotherapy (RT); RT and cytostatics; or decortication plus RT plus cytostatics. The median survival (MS) from diagnosis was 9.6 months. This was similar for all comparable treatment groups. In a univariate analysis, significant favorable prognostic factors were good performance status (PS), duration of symptoms greater than 6 months at the time of diagnosis, early stage of disease, white race, and female sex. In a multivariate analysis, PS, race, duration of symptoms, and stage were of significance for a favorable prognosis. Age, pain as first symptom, histologic subtype, and RT dose were not of prognosis significance in this study. The stepwise addition of treatment modalities did not increase survival, which remained the same as that reported for untreated patients. Therefore, phase II trials of new agents offer the only hope for advance in the treatment of this disease.

Thirty-three patients with advanced colorectal cancer were entered on a phase II study of 4'-deoxydoxorubicin (esorubicin) (30-35 mg/m2 q 3 weekly). Objective response was documented in 4 of 25 previously untreated patients and in none of 8 previously treated patients. Toxicity was acceptable with grade 3 or 4 leukopenia occurring in 8 patients. Complete alopecia occurred only in 4 patients and gastro-intestinal toxicity was mild. A significant decrease (greater than 10%) of the left ventricular ejection fraction occurred in 8/23 patients who received greater than 2 courses of treatment.

Twenty-two patients with histologically confirmed non-Hodgkin's lymphoma received treatment with a chemotherapy combination containing cyclophosphamide, mitoxantrone, vincristine and prednisone. Leukopenia, nausea and vomiting were the most common side effects. A response rate of 77% (17 of 22 patients) was documented. These results indicate that the four-drug combination including mitoxantrone has good therapeutic activity in the treatment of non-Hodgkin's lymphoma.

Serial assessment of ventricular function by means of radionuclide angiography was performed in 50 patients with malignant neoplasms who received either 4'-epidoxorubicin or mitoxantrone for longer than 3 months. In 9 of 30 patients given 4'-epidoxorubicin, a decrease of greater than or equal to 10% in the left ventricular ejection fraction (LVEF) was documented at doses of 143-1200 mg/m2. Two patients developed clinical signs of cardiotoxicity at a dose of greater than 1000 mg/m2. In 6 of 20 patients given mitoxantrone a decrease of greater than or equal to 10% in the LVEF occurred at doses of 26-98 mg/m2.

Forty-six patients with acute leukemia were treated with mitoxantrone as a single agent. Twenty-nine patients had relapsed and/or refractory acute leukemia. Seventeen patients with acute non-lymphatic leukemia had received no prior treatment. Twelve mg/m2 of mitoxantrone was given intravenous on five consecutive days. Treatment related side effects included bone marrow suppression, mucositis, alopecia, nausea, vomiting and infection. Cardiotoxicity was documented in 7 patients. This study reconfirms that mitoxantrone is an active agent in acute leukemia with complete response documented in 10 of 29 patients with relapsed and/or refractory acute leukemia (34% response rate, 95% confidence limits 18-53%) and complete response documented in 11 of 17 patients (65% response rate, 95% confidence limits 38-87%) with previously untreated acute nonlymphatic leukemia.

A case of cardiotoxicity caused by 5-fluoro-uracil administration is described. The aetiological process is not clear, and it is possible that 5-fluoro-uracil has a vasoconstrictive effect on the coronary artery system.

Twenty-six previously untreated patients with acute non-lymphocytic leukemia (ANLL) were treated with oral idarubicin and cytosine-arabinoside (Ara-C). The median age of the patients was 44 years (range, 11-72). In 23 of the 26 patients a hypoplastic marrow, with a peripheral white cell count of less than 1,000/mm3 after treatment, was documented. Treatment was well tolerated with minimal symptoms of nausea and vomiting. Diarrhea was observed in three patients and stomatitis in nine patients. Alopecia was documented in only six patients. A complete remission (CR) was obtained in 12 patients (median duration 25 weeks). The median time to CR was 3.4 weeks (range, 1.4-5). Ten of the 26 patients were alive 6 months after the start of induction treatment, while a further four patients who were in the study for less than 6 months are alive and in remission at 5, 4, 3, and 3 months, respectively. Eight of 12 patients in whom bone marrow aplasia was documented achieved a CR; perhaps the drug dosages used in this study were suboptimal.

Serial assessment of ventricular function by means of a nuclear medicine technique was performed in six patients with malignant disease receiving chemotherapy with amsacrine. Two patients who received treatment long enough so that greater than 580 mg/m2 of the drug was administered showed a significant decrease in left ventricular ejection fraction. Four patients who received total doses of 325-510 mg/m2 of amsacrine did not experience significant change in their cardiac function.

A patient with chronic granulocytic leukemia, neutrophilic type, was followed for 28 months. A paraproteinemia, IgA type K, and Bence Jones proteinuria (K) appeared without prior chemotherapy with alkylating agents.