Chemotherapy for Late-Stage Cancer Patients: Meta-Analysis of Complete Response Rates

Complete response (CR) rates reported for cytotoxic chemotherapy for late-stage cancer patients are generally low, with few exceptions, regardless of the solid cancer type or drug regimen. We investigated CR rates reported in the literature for clinical trials using chemotherapy alone, across a wide range of tumour types and chemotherapeutic regimens, to determine an overall CR rate for late-stage cancers. A total of 141 reports were located using the PubMed database. A meta-analysis was performed of reported CR from 68 chemotherapy trials (total 2732 patients) using standard agents across late-stage solid cancers—a binomial model with random effects was adopted. Mean CR rates were compared for different cancer types, and for chemotherapeutic agents with different mechanisms of action, using a logistic regression. Our results showed that the CR rates for chemotherapy treatment of late-stage cancer were generally low at 7.4%, regardless of the cancer type or drug regimen used. We found no evidence that CR rates differed between different chemotherapy drug types, but amongst different cancer types small CR differences were evident, although none exceeded a mean CR rate of 11%. This remarkable concordance of CR rates regardless of cancer or therapy type remains currently unexplained, and motivates further investigation.

[1]  N. André,et al.  Metronomics: towards personalized chemotherapy? , 2014, Nature Reviews Clinical Oncology.

[2]  P. Hersey,et al.  Prolonged repeated vaccine immuno-chemotherapy induces long-term clinical responses and survival for advanced metastatic melanoma , 2014, Journal of Immunotherapy for Cancer.

[3]  I. Voutsadakis The chemosensitivity of testicular germ cell tumors , 2014, Cellular Oncology.

[4]  Silas W Smith,et al.  An approach to chemotherapy-associated toxicity. , 2014, Emergency medicine clinics of North America.

[5]  Gábor Balázsi,et al.  Network of mutually repressive metastasis regulators can promote cell heterogeneity and metastatic transitions , 2014, Proceedings of the National Academy of Sciences.

[6]  J. Whitlock,et al.  Recent advances in acute lymphoblastic leukemia in children and adolescents: an expert panel discussion , 2013, Current opinion in oncology.

[7]  A. Napper,et al.  Targeted Drug Discovery for Pediatric Leukemia , 2013, Front. Oncol..

[8]  C. Chao,et al.  Cancer cells acquire resistance to anticancer drugs: an update. , 2012, Biomedical journal.

[9]  B. Coventry,et al.  The 20th anniversary of interleukin-2 therapy: bimodal role explaining longstanding random induction of complete clinical responses , 2012, Cancer management and research.

[10]  B. Coventry,et al.  Complete clinical responses to cancer therapy caused by multiple divergent approaches: a repeating theme lost in translation , 2012, Cancer management and research.

[11]  D. Berney,et al.  Testing testes: problems and recent advances in the diagnosis of testicular tumours and implications for treatment. , 2012, Clinical oncology (Royal College of Radiologists (Great Britain)).

[12]  R. Tuma Large trials, small gains: is change on the way? , 2010, Journal of the National Cancer Institute.

[13]  E. Winer,et al.  International Guidelines for Management of Metastatic Breast Cancer: Can Metastatic Breast Cancer Be Cured? , 2010, Journal of the National Cancer Institute.

[14]  M. Quinn,et al.  CRP identifies homeostatic immune oscillations in cancer patients: a potential treatment targeting tool? , 2009, Journal of Translational Medicine.

[15]  D. Klatzmann,et al.  Tumor emergence is sensed by self-specific CD44hi memory Tregs that create a dominant tolerogenic environment for tumors in mice. , 2009, The Journal of clinical investigation.

[16]  D. Moher,et al.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement , 2009, BMJ : British Medical Journal.

[17]  Aaron M. Schmidt,et al.  A matter of time: individual differences, contextual dynamics, and goal progress effects on multiple-goal self-regulation. , 2009, The Journal of applied psychology.

[18]  Julian Little,et al.  Systematic Reviews of Genetic Association Studies , 2009, PLoS medicine.

[19]  Nicola Bellomo,et al.  On the foundations of cancer modelling: Selected topics, speculations, and perspectives , 2008 .

[20]  Donna Niedzwiecki,et al.  Meta-analysis of phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future phase II trials. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  R. Thomas,et al.  Weekly cisplatin, epirubicin, and paclitaxel with granulocyte colony-stimulating factor support vs triweekly epirubicin and paclitaxel in locally advanced breast cancer: final analysis of a sicog phase III study , 2006, British Journal of Cancer.

[22]  S. Yang,et al.  Temozolomide Chemotherapy in Patients with Recurrent Malignant Gliomas , 2006, Journal of Korean medical science.

[23]  K. McMasters,et al.  A phase II study of extended dose temozolomide and thalidomide in previously treated patients with metastatic melanoma , 2006, Journal of Cancer Research and Clinical Oncology.

[24]  Y. Shimada,et al.  Phase II study of combination therapy with S-1 and irinotecan in patients with advanced colorectal cancer. , 2006, Annals of oncology : official journal of the European Society for Medical Oncology.

[25]  J. Menell,et al.  Phase II study of temozolomide plus pegylated interferon‐α‐2b for metastatic melanoma , 2006 .

[26]  John Travis,et al.  Celebrating a Glass Half-Full , 2006, Science.

[27]  M. Caraglia,et al.  Weekly oxaliplatin, 5-fluorouracil and folinic acid (OXALF) as first-line chemotherapy for elderly patients with advanced gastric cancer: results of a phase II trial , 2006, BMC Cancer.

[28]  D. Galetta,et al.  Sequential chemotherapy with cisplatin/gemcitabine (CG) followed by mitoxantrone/methotrexate/mitomycin (MMM) in patients with malignant pleural mesothelioma. A multicenter Italian Phase II Study (SITMP1). , 2006, Lung cancer.

[29]  S. Sohn,et al.  Phase II study of capecitabine and irinotecan combination chemotherapy in patients with advanced gastric cancer , 2006, British Journal of Cancer.

[30]  J. Feliu,et al.  XELOX (capecitabine plus oxaliplatin) as first-line treatment for elderly patients over 70 years of age with advanced colorectal cancer , 2006, British Journal of Cancer.

[31]  D. Dunlop,et al.  Phase II study of gemcitabine and cisplatin in locally advanced/metastatic oesophageal cancer , 2005, British Journal of Cancer.

[32]  J. Sorosky,et al.  Phase II trial of dacarbazine, mitomycin, doxorubicin, and cisplatin with sargramostim in uterine leiomyosarcoma: a Gynecologic Oncology Group study. , 2005, Gynecologic Oncology.

[33]  N. Tsavaris,et al.  A Phase II Study of the Docetaxel–Carboplatin Chemotherapy Regimen in Advanced Non-Small-Cell Lung Cancer , 2005, Lung.

[34]  B. Gustavsson,et al.  Phase I/II trial of intraperitoneal 5-Fluorouracil with and without intravenous Vasopressin in non-resectable pancreas cancer , 2005, Cancer Chemotherapy and Pharmacology.

[35]  Derek Abbott,et al.  Modeling the effect of p53 on tumor heterogeneity and the mutator phenotype , 2005, SPIE Micro + Nano Materials, Devices, and Applications.

[36]  N. Savaraj,et al.  Cyclosporine A, Alpha-Interferon and Interleukin-2 Following Chemotherapy with BCNU, DTIC, Cisplatin, and Tamoxifen: A Phase II Study in Advanced Melanoma , 2005, Cancer investigation.

[37]  Graeme Morgan,et al.  The contribution of cytotoxic chemotherapy to 5-year survival in adult malignancies. , 2004, Clinical oncology (Royal College of Radiologists (Great Britain)).

[38]  M. Inbar,et al.  Phase II study of weekly topotecan in patients with recurrent or persistent epithelial ovarian cancer. , 2004, Gynecologic oncology.

[39]  P. Kountourakis,et al.  Oxaliplatin plus high-dose leucovorin and 5-fluorouracil (FOLFOX 4) in platinum-resistant and taxane-pretreated ovarian cancer: a phase II study. , 2004, Gynecologic oncology.

[40]  Y. Hashiguchi,et al.  Phase I–II study of irinotecan (CPT-11) plus nedaplatin (254-S) with recombinant human granulocyte colony-stimulating factor support in patients with advanced or recurrent cervical cancer , 2004, British Journal of Cancer.

[41]  B. Monk,et al.  Cisplatin and irinotecan in squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. , 2004, Gynecologic oncology.

[42]  E. Perez,et al.  Randomized phase II study of two irinotecan schedules for patients with metastatic breast cancer refractory to an anthracycline, a taxane, or both. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[43]  D. Alberts,et al.  Tirapazamine plus cisplatin in advanced or recurrent carcinoma of the uterine cervix: a Southwest Oncology Group study , 2004, International Journal of Gynecologic Cancer.

[44]  E. Perez,et al.  Phase II study of oral etoposide and intravenous paclitaxel in extensive-stage small cell lung cancer. , 2004, Lung cancer.

[45]  J. Berlin,et al.  Phase II Study of Gemcitabine in Combination with Docetaxel in Patients with Advanced Pancreatic Carcinoma (E1298) , 2004, Oncology.

[46]  Derek Abbott,et al.  Fluctuations and noise in cancer development , 2004, SPIE International Symposium on Fluctuations and Noise.

[47]  S. Spencer,et al.  An ordinary differential equation model for the multistep transformation to cancer. , 2004, Journal of theoretical biology.

[48]  S. Choi,et al.  Phase II Study of Gemcitabine Combined with Uracil-Tegafur in Metastatic Pancreatic Cancer , 2004, Oncology.

[49]  L. Mariani,et al.  Randomized multicenter Phase II trial of two different schedules of irinotecan combined with capecitabine as first‐line treatment in metastatic colorectal carcinoma , 2004, Cancer.

[50]  S. Dakhil,et al.  A Phase II Evaluation of Weekly Paclitaxel Plus Carboplatin in Advanced Urothelial Cancer , 2004, Cancer investigation.

[51]  Hyae-Young Kim,et al.  A Phase II study of weekly irinotecan and capecitabine in patients with previously treated non-small cell lung cancer. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[52]  M. Morgan,et al.  Phase II study of oxaliplatin in platinum-resistant and refractory ovarian cancer: a gynecologic group study. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[53]  J. Aparicio,et al.  A multicenter phase II study of irinotecan (CPT-11) alternated with 5-fluorouracil and leucovorin as first-line treatment of patients with metastatic colorectal cancer , 2003, Cancer Chemotherapy and Pharmacology.

[54]  M. Nicolson,et al.  A phase II study of mitomycin C, cisplatin and protracted infusional 5-fluorouracil in advanced pancreatic carcinoma: efficacy and low toxicity. , 2003, Annals of oncology : official journal of the European Society for Medical Oncology.

[55]  M. Dimopoulos,et al.  Phase II study of docetaxel-vinorelbine in platinum-resistant, paclitaxel-pretreated ovarian cancer. , 2003, Annals of oncology : official journal of the European Society for Medical Oncology.

[56]  A. Koletsky,et al.  Phase II Study of Vinorelbine and Low‐Dose Docetaxel in Chemotherapy‐Naive Patients with Hormone‐Refractory Prostate Cancer , 2003, Cancer journal.

[57]  Susan M. Chang,et al.  Phase II evaluation of temozolomide and 13-cis-retinoic acid for the treatment of recurrent and progressive malignant glioma: a North American Brain Tumor Consortium study. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[58]  I. Chitapanarux,et al.  Phase II clinical study of irinotecan and cisplatin as first-line chemotherapy in metastatic or recurrent cervical cancer. , 2003, Gynecologic oncology.

[59]  J. Sham,et al.  A phase II study of capecitabine in patients with recurrent and metastatic nasopharyngeal carcinoma pretreated with platinum-based chemotherapy. , 2003, Oral oncology.

[60]  J. Pintos,et al.  Weekly paclitaxel and gemcitabine chemotherapy for metastatic non‐small cell lung carcinoma (NSCLC) , 2003, Cancer.

[61]  P. Rose,et al.  A phase II study of docetaxel in paclitaxel-resistant ovarian and peritoneal carcinoma: a Gynecologic Oncology Group study. , 2003, Gynecologic oncology.

[62]  D. Bodurka,et al.  Phase II trial of irinotecan in patients with metastatic epithelial ovarian cancer or peritoneal cancer. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[63]  I. Tannock,et al.  Chemotherapy with gemcitabine‐containing regimens for locally recurrent or metastatic nasopharyngeal carcinoma , 2002, Cancer.

[64]  J. Kim,et al.  Phase II study of capecitabine plus cisplatin as first-line chemotherapy in advanced biliary cancer. , 2002, Annals of oncology : official journal of the European Society for Medical Oncology.

[65]  E. Espinosa,et al.  A phase II trial of cisplatin and vinorelbine in patients with recurrent or metastatic squamous cell carcinoma of the head and neck , 2002, Head & neck.

[66]  H. Gogas,et al.  Docetaxel in Combination with Dacarbazine in Patients with Advanced Melanoma , 2002, Oncology.

[67]  G. Sledge,et al.  Combined anti-microtubule therapy: a phase II study of weekly docetaxel plus estramustine in patients with metastatic breast cancer. , 2002, Annals of oncology : official journal of the European Society for Medical Oncology.

[68]  L. Fioretto,et al.  Weekly gemcitabine plus Epirubicin as effective chemotherapy for advanced pancreatic cancer: a multicenter phase II study , 2002, British Journal of Cancer.

[69]  M. Ducreux,et al.  Optimization of 5-fluorouracil (5-FU)/cisplatin combination chemotherapy with a new schedule of leucovorin, 5-FU and cisplatin (LV5FU2-P regimen) in patients with biliary tract carcinoma. , 2002, Annals of oncology : official journal of the European Society for Medical Oncology.

[70]  A. Avallone,et al.  Oxaliplatin plus raltitrexed and leucovorin-modulated 5-fluorouracil i.v. bolus: a salvage regimen for colorectal cancer patients , 2002, British Journal of Cancer.

[71]  D. Miller,et al.  Phase II study of mitomycin, doxorubicin, and cisplatin in the treatment of advanced uterine leiomyosarcoma: a Gynecologic Oncology Group study. , 2002, Gynecologic oncology.

[72]  E. Cho,et al.  Epirubicin, cisplatin, and protracted venous infusion of 5-fluorouracil for advanced gastric carcinoma. , 2002, Journal of Korean medical science.

[73]  Jun Suk Kim,et al.  A Phase II study of paclitaxel by 24‐hour infusion and ifosfamide in anthracycline‐resistant metastatic breast carcinoma , 2002, Cancer.

[74]  P. Garrido,et al.  Ifosfamide and vinorelbine in advanced platinum-resistant ovarian cancer: excessive toxicity with a potentially active regimen. , 2002, Gynecologic oncology.

[75]  C. Tropé,et al.  Phase I/II trial of the multidrug-resistance modulator valspodar combined with cisplatin and doxorubicin in refractory ovarian cancer. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[76]  V. Gebbia,et al.  Cisplatin and vinorelbine in advanced and/or metastatic adenocarcinoma of the endometrium: a new highly active chemotherapeutic regimen. , 2001, Annals of oncology : official journal of the European Society for Medical Oncology.

[77]  A. Monnier,et al.  Combined paclitaxel and gemcitabine as first-line treatment in metastatic non-small cell lung cancer: a multicentre phase II study , 2001, British Journal of Cancer.

[78]  S. Lippman,et al.  Phase II study of paclitaxel, ifosfamide, and carboplatin in patients with recurrent or metastatic head and neck squamous cell carcinoma , 2001, Cancer.

[79]  P. Chen,et al.  Tamoxifen and colchicine-modulated vinblastine followed by 5-fluorouracil in advanced renal cell carcinoma: a phase II study. , 2001, Urology.

[80]  R. Schilsky,et al.  Phase II study of oral eniluracil, 5‐fluorouracil, and leucovorin in patients with advanced colorectal carcinoma , 2001, Cancer.

[81]  M. Airoldi,et al.  Phase II randomized trial comparing vinorelbine versus vinorelbine plus cisplatin in patients with recurrent salivary gland malignancies , 2001, Cancer.

[82]  A. Lluch,et al.  Doxorubicin and paclitaxel in advanced breast carcinoma , 2000, Cancer.

[83]  V. Heinemann,et al.  Gemcitabine and cisplatin in the treatment of advanced or metastatic pancreatic cancer. , 2000, Annals of oncology : official journal of the European Society for Medical Oncology.

[84]  G. Cocconi,et al.  Vinorelbine combined with paclitaxel infused over 96 hours (VI‐TA‐96) for patients with metastatic breast carcinoma , 2000, Cancer.

[85]  W. Oh,et al.  Phase II trial of gemcitabine plus cisplatin in patients with metastatic urothelial cancer. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[86]  B. Leyland-Jones,et al.  A phase II trial of mitomycin, ifosfamide and cisplatin in recurrent carcinoma of the cervix. , 2000, International journal of gynecological cancer : official journal of the International Gynecological Cancer Society.

[87]  M. van Glabbeke,et al.  New guidelines to evaluate the response to treatment in solid tumors , 2000, Journal of the National Cancer Institute.

[88]  M. Khoury,et al.  The Human Genome Epidemiology Network. , 1998, American journal of epidemiology.

[89]  G. Smith,et al.  Bias in meta-analysis detected by a simple, graphical test , 1997, BMJ.

[90]  J. Bauer A matter of time. , 1995, Journal of post anesthesia nursing.

[91]  C. Begg,et al.  Operating characteristics of a rank correlation test for publication bias. , 1994, Biometrics.

[92]  Henderson Ic Window of opportunity. , 1991 .

[93]  M. Awwad,et al.  Cyclophosphamide-induced immunologically mediated regression of a cyclophosphamide-resistant murine tumor: a consequence of eliminating precursor L3T4+ suppressor T-cells. , 1989, Cancer research.

[94]  S. El-Mesidi,et al.  A phase II study of gemcitabine combined with vinorelbine as first-line chemotherapy for metastatic breast cancer. , 2010, Hematology/oncology and stem cell therapy.

[95]  H. Kalofonos,et al.  Combination docetaxel (Taxotere), fluorouracil, and leucovorin (TFL), as first-line chemotherapy in advanced gastric cancer: a Hellenic Cooperative Oncology Group phase II study , 2005, Gastric Cancer.

[96]  D. Miller,et al.  Phase II evaluation of 9-aminocamptothecin (9-AC, NSC #603071) in platinum-resistant ovarian and primary peritoneal carcinoma: a Gynecologic Oncology Group Study. , 2005, Gynecologic oncology.

[97]  D. Furst Window of opportunity. , 2004, Journal of Rheumatology.

[98]  M. González-Barón,et al.  Phase II trial of vinorelbine and estramustine in the treatment of metastatic hormone-resistant prostate cancer. , 2004, Urologic oncology.

[99]  G. Scambia,et al.  Phase II study of pegylated liposomal doxorubicin in heavily pretreated epithelial ovarian cancer patients. May a new treatment schedule improve toxicity profile? , 2004, Oncology.

[100]  S. Yoshida,et al.  A Phase II study of irinotecan in combination with 120-h infusion of 5-fluorouracil in patients with metastatic colorectal carcinoma: Japan Clinical Oncology Group Study (JCOG9703). , 2003, Japanese journal of clinical oncology.

[101]  T. Delozier,et al.  Phase II study of oral vinorelbine in first-line advanced breast cancer chemotherapy. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[102]  M. Bookman,et al.  Phase II trial of pyrazoloacridine in recurrent platinum-sensitive ovarian cancer: a Gynecologic Oncology Group study. , 2002, Gynecologic oncology.

[103]  S. Yoshida,et al.  A Phase II Study of Irinotecan in Combination with 120-h Infusion of 5-Fluorouracil in Patients with Metastatic Colorectal Carcinoma : Japan Clinical Oncology Group Study ( JCOG 9703 ) , 2002 .

[104]  M Van Glabbeke,et al.  New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. , 2000, Journal of the National Cancer Institute.

[105]  J C Bailar,et al.  Cancer undefeated. , 1997, The New England journal of medicine.

[106]  T. Beardsley A war not won. , 1994, Scientific American.