Loading…

A randomised trial of planned versus as required chemotherapy in small cell lung cancer: a Cancer Research Campaign trial

In a study of chemotherapy as palliative treatment, 300 patients with untreated limited and extensive stage small cell lung cancer (SCLC), who did not have progressive disease after the first cycle of chemotherapy, were randomised to receive either regular 'planned' chemotherapy or chemoth...

Full description

Saved in:
Bibliographic Details
Published in:British journal of cancer 1991-09, Vol.64 (3), p.566-572
Main Authors: EARL, H. M, RUDD, R. M, PARTRIDGE, M. R, SOUHAMI, R. L, SPIRO, S. G, ASH, C. M, JAMES, L. E, LAW, C. S, TOBIAS, J. S, HARPER, P. G, GEDDES, D. M, ERAUT, D
Format: Article
Language:English
Subjects:
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c433t-250f8c85dc2b50164c4636410e39cccb6eb4f14baf1b52edff40afa4f010cf643
cites
container_end_page 572
container_issue 3
container_start_page 566
container_title British journal of cancer
container_volume 64
creator EARL, H. M
RUDD, R. M
PARTRIDGE, M. R
SOUHAMI, R. L
SPIRO, S. G
ASH, C. M
JAMES, L. E
LAW, C. S
TOBIAS, J. S
HARPER, P. G
GEDDES, D. M
ERAUT, D
description In a study of chemotherapy as palliative treatment, 300 patients with untreated limited and extensive stage small cell lung cancer (SCLC), who did not have progressive disease after the first cycle of chemotherapy, were randomised to receive either regular 'planned' chemotherapy or chemotherapy given 'as required' (AR). All patients received the same chemotherapy: cyclophosphamide 1 gm m-2 i.v., vincristine 2 mg i.v., and etoposide 120 mg m-2 i.v. on day 1, and etoposide 100 mg b.d. orally on days 2 and 3. Planned chemotherapy was given regularly every 3 weeks. AR chemotherapy was given for tumour-related symptoms, or for radiological progression of disease. Both groups of patients were assessed every 3 weeks and a maximum of eight cycles of chemotherapy was given. A detailed quality of life assessment was made using daily diary cards. The median survival (MS) of patients given AR chemotherapy was not significantly worse than those receiving planned treatment [MS: Planned = 36 weeks (95% C.I. 32-40 weeks), AR = 32 weeks (95% C.I. 28-37 weeks) P = 0.960]. In the AR patients the median interval between treatments was 42 days. On average AR patients received half as much chemotherapy as planned patients. AR patients with a treatment-free interval (TFI) of more than 8 weeks between the first and second cycles of chemotherapy survived longer than those in whom this interval was less than 4 weeks; [MS: TFI greater than 8 = 47 weeks (95% C.I. 32-53 weeks); TFI less than 4 = 24 weeks (95% C.I. 17-34 weeks) P = 0.013]. Contrary to expectation, in the quality of life assessment the AR patients scored themselves as having more severe symptoms than patients receiving planned treatment. AR chemotherapy is a novel method of attempting to use cytotoxic drugs palliatively, which resulted in less drug treatment for approximately equivalent survival. However the palliative effect seen with as required treatment was less satisfactory than with planned chemotherapy.
doi_str_mv 10.1038/bjc.1991.351
format article
fullrecord <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1977632</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1654983</sourcerecordid><originalsourceid>FETCH-LOGICAL-c433t-250f8c85dc2b50164c4636410e39cccb6eb4f14baf1b52edff40afa4f010cf643</originalsourceid><addsrcrecordid>eNpVUU1r3DAQFaUl3aa99VrQocd4qy9_5RAIS9oGAoGQnMV4LO0q2LIj2YH999HWYdNcRjPznt6DeYR852zNmax-NY-45nXN1zLnH8iK51JkvBLlR7JijJUZqwX7TL7E-JjGmlXlCTnhRa7qSq7I_pIG8O3Qu2haOgUHHR0sHTvwPi2eTYhzpBBpME-zC2mFO9MP084EGPfUeRp76DqKJpVu9luK4NGEcwp086-jdyYaCLhLcz-C2_rF5iv5ZKGL5tvre0oefl_db_5mN7d_rjeXNxkqKadM5MxWWOUtiiZnvFCoClkozoysEbEpTKMsVw1Y3uTCtNYqBhaUZZyhLZQ8JReL7jg3vWnR-ClAp8fgegh7PYDT7xHvdno7PGtel2UhRRI4WwQwDDEGY49_OdOHBHRKQB8S0CmBRP_xv98beTl5wn--4hAROpvOjy4eaXkKSYgi0ehC8zDNwRzx5HWwOji9AKtFnHQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>A randomised trial of planned versus as required chemotherapy in small cell lung cancer: a Cancer Research Campaign trial</title><source>PubMed Central Free</source><creator>EARL, H. M ; RUDD, R. M ; PARTRIDGE, M. R ; SOUHAMI, R. L ; SPIRO, S. G ; ASH, C. M ; JAMES, L. E ; LAW, C. S ; TOBIAS, J. S ; HARPER, P. G ; GEDDES, D. M ; ERAUT, D</creator><creatorcontrib>EARL, H. M ; RUDD, R. M ; PARTRIDGE, M. R ; SOUHAMI, R. L ; SPIRO, S. G ; ASH, C. M ; JAMES, L. E ; LAW, C. S ; TOBIAS, J. S ; HARPER, P. G ; GEDDES, D. M ; ERAUT, D</creatorcontrib><description>In a study of chemotherapy as palliative treatment, 300 patients with untreated limited and extensive stage small cell lung cancer (SCLC), who did not have progressive disease after the first cycle of chemotherapy, were randomised to receive either regular 'planned' chemotherapy or chemotherapy given 'as required' (AR). All patients received the same chemotherapy: cyclophosphamide 1 gm m-2 i.v., vincristine 2 mg i.v., and etoposide 120 mg m-2 i.v. on day 1, and etoposide 100 mg b.d. orally on days 2 and 3. Planned chemotherapy was given regularly every 3 weeks. AR chemotherapy was given for tumour-related symptoms, or for radiological progression of disease. Both groups of patients were assessed every 3 weeks and a maximum of eight cycles of chemotherapy was given. A detailed quality of life assessment was made using daily diary cards. The median survival (MS) of patients given AR chemotherapy was not significantly worse than those receiving planned treatment [MS: Planned = 36 weeks (95% C.I. 32-40 weeks), AR = 32 weeks (95% C.I. 28-37 weeks) P = 0.960]. In the AR patients the median interval between treatments was 42 days. On average AR patients received half as much chemotherapy as planned patients. AR patients with a treatment-free interval (TFI) of more than 8 weeks between the first and second cycles of chemotherapy survived longer than those in whom this interval was less than 4 weeks; [MS: TFI greater than 8 = 47 weeks (95% C.I. 32-53 weeks); TFI less than 4 = 24 weeks (95% C.I. 17-34 weeks) P = 0.013]. Contrary to expectation, in the quality of life assessment the AR patients scored themselves as having more severe symptoms than patients receiving planned treatment. AR chemotherapy is a novel method of attempting to use cytotoxic drugs palliatively, which resulted in less drug treatment for approximately equivalent survival. However the palliative effect seen with as required treatment was less satisfactory than with planned chemotherapy.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/bjc.1991.351</identifier><identifier>PMID: 1654983</identifier><identifier>CODEN: BJCAAI</identifier><language>eng</language><publisher>Basingstoke: Nature Publishing Group</publisher><subject>Aged ; Antineoplastic agents ; Antineoplastic Combined Chemotherapy Protocols - administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biological and medical sciences ; Carcinoma, Small Cell - drug therapy ; Carcinoma, Small Cell - pathology ; Chemotherapy ; Cyclophosphamide - administration &amp; dosage ; Drug Administration Schedule ; Etoposide - administration &amp; dosage ; Female ; Humans ; Lung Neoplasms - drug therapy ; Lung Neoplasms - pathology ; Male ; Medical sciences ; Middle Aged ; Neoplasm Staging ; Pharmacology. Drug treatments ; Quality of Life ; Vincristine - administration &amp; dosage</subject><ispartof>British journal of cancer, 1991-09, Vol.64 (3), p.566-572</ispartof><rights>1992 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c433t-250f8c85dc2b50164c4636410e39cccb6eb4f14baf1b52edff40afa4f010cf643</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1977632/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1977632/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=5000226$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1654983$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>EARL, H. M</creatorcontrib><creatorcontrib>RUDD, R. M</creatorcontrib><creatorcontrib>PARTRIDGE, M. R</creatorcontrib><creatorcontrib>SOUHAMI, R. L</creatorcontrib><creatorcontrib>SPIRO, S. G</creatorcontrib><creatorcontrib>ASH, C. M</creatorcontrib><creatorcontrib>JAMES, L. E</creatorcontrib><creatorcontrib>LAW, C. S</creatorcontrib><creatorcontrib>TOBIAS, J. S</creatorcontrib><creatorcontrib>HARPER, P. G</creatorcontrib><creatorcontrib>GEDDES, D. M</creatorcontrib><creatorcontrib>ERAUT, D</creatorcontrib><title>A randomised trial of planned versus as required chemotherapy in small cell lung cancer: a Cancer Research Campaign trial</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><description>In a study of chemotherapy as palliative treatment, 300 patients with untreated limited and extensive stage small cell lung cancer (SCLC), who did not have progressive disease after the first cycle of chemotherapy, were randomised to receive either regular 'planned' chemotherapy or chemotherapy given 'as required' (AR). All patients received the same chemotherapy: cyclophosphamide 1 gm m-2 i.v., vincristine 2 mg i.v., and etoposide 120 mg m-2 i.v. on day 1, and etoposide 100 mg b.d. orally on days 2 and 3. Planned chemotherapy was given regularly every 3 weeks. AR chemotherapy was given for tumour-related symptoms, or for radiological progression of disease. Both groups of patients were assessed every 3 weeks and a maximum of eight cycles of chemotherapy was given. A detailed quality of life assessment was made using daily diary cards. The median survival (MS) of patients given AR chemotherapy was not significantly worse than those receiving planned treatment [MS: Planned = 36 weeks (95% C.I. 32-40 weeks), AR = 32 weeks (95% C.I. 28-37 weeks) P = 0.960]. In the AR patients the median interval between treatments was 42 days. On average AR patients received half as much chemotherapy as planned patients. AR patients with a treatment-free interval (TFI) of more than 8 weeks between the first and second cycles of chemotherapy survived longer than those in whom this interval was less than 4 weeks; [MS: TFI greater than 8 = 47 weeks (95% C.I. 32-53 weeks); TFI less than 4 = 24 weeks (95% C.I. 17-34 weeks) P = 0.013]. Contrary to expectation, in the quality of life assessment the AR patients scored themselves as having more severe symptoms than patients receiving planned treatment. AR chemotherapy is a novel method of attempting to use cytotoxic drugs palliatively, which resulted in less drug treatment for approximately equivalent survival. However the palliative effect seen with as required treatment was less satisfactory than with planned chemotherapy.</description><subject>Aged</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Combined Chemotherapy Protocols - administration &amp; dosage</subject><subject>Antineoplastic Combined Chemotherapy Protocols - adverse effects</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Small Cell - drug therapy</subject><subject>Carcinoma, Small Cell - pathology</subject><subject>Chemotherapy</subject><subject>Cyclophosphamide - administration &amp; dosage</subject><subject>Drug Administration Schedule</subject><subject>Etoposide - administration &amp; dosage</subject><subject>Female</subject><subject>Humans</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neoplasm Staging</subject><subject>Pharmacology. Drug treatments</subject><subject>Quality of Life</subject><subject>Vincristine - administration &amp; dosage</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><recordid>eNpVUU1r3DAQFaUl3aa99VrQocd4qy9_5RAIS9oGAoGQnMV4LO0q2LIj2YH999HWYdNcRjPznt6DeYR852zNmax-NY-45nXN1zLnH8iK51JkvBLlR7JijJUZqwX7TL7E-JjGmlXlCTnhRa7qSq7I_pIG8O3Qu2haOgUHHR0sHTvwPi2eTYhzpBBpME-zC2mFO9MP084EGPfUeRp76DqKJpVu9luK4NGEcwp086-jdyYaCLhLcz-C2_rF5iv5ZKGL5tvre0oefl_db_5mN7d_rjeXNxkqKadM5MxWWOUtiiZnvFCoClkozoysEbEpTKMsVw1Y3uTCtNYqBhaUZZyhLZQ8JReL7jg3vWnR-ClAp8fgegh7PYDT7xHvdno7PGtel2UhRRI4WwQwDDEGY49_OdOHBHRKQB8S0CmBRP_xv98beTl5wn--4hAROpvOjy4eaXkKSYgi0ehC8zDNwRzx5HWwOji9AKtFnHQ</recordid><startdate>19910901</startdate><enddate>19910901</enddate><creator>EARL, H. M</creator><creator>RUDD, R. M</creator><creator>PARTRIDGE, M. R</creator><creator>SOUHAMI, R. L</creator><creator>SPIRO, S. G</creator><creator>ASH, C. M</creator><creator>JAMES, L. E</creator><creator>LAW, C. S</creator><creator>TOBIAS, J. S</creator><creator>HARPER, P. G</creator><creator>GEDDES, D. M</creator><creator>ERAUT, D</creator><general>Nature Publishing Group</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>19910901</creationdate><title>A randomised trial of planned versus as required chemotherapy in small cell lung cancer: a Cancer Research Campaign trial</title><author>EARL, H. M ; RUDD, R. M ; PARTRIDGE, M. R ; SOUHAMI, R. L ; SPIRO, S. G ; ASH, C. M ; JAMES, L. E ; LAW, C. S ; TOBIAS, J. S ; HARPER, P. G ; GEDDES, D. M ; ERAUT, D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c433t-250f8c85dc2b50164c4636410e39cccb6eb4f14baf1b52edff40afa4f010cf643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>Aged</topic><topic>Antineoplastic agents</topic><topic>Antineoplastic Combined Chemotherapy Protocols - administration &amp; dosage</topic><topic>Antineoplastic Combined Chemotherapy Protocols - adverse effects</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Small Cell - drug therapy</topic><topic>Carcinoma, Small Cell - pathology</topic><topic>Chemotherapy</topic><topic>Cyclophosphamide - administration &amp; dosage</topic><topic>Drug Administration Schedule</topic><topic>Etoposide - administration &amp; dosage</topic><topic>Female</topic><topic>Humans</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neoplasm Staging</topic><topic>Pharmacology. Drug treatments</topic><topic>Quality of Life</topic><topic>Vincristine - administration &amp; dosage</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>EARL, H. M</creatorcontrib><creatorcontrib>RUDD, R. M</creatorcontrib><creatorcontrib>PARTRIDGE, M. R</creatorcontrib><creatorcontrib>SOUHAMI, R. L</creatorcontrib><creatorcontrib>SPIRO, S. G</creatorcontrib><creatorcontrib>ASH, C. M</creatorcontrib><creatorcontrib>JAMES, L. E</creatorcontrib><creatorcontrib>LAW, C. S</creatorcontrib><creatorcontrib>TOBIAS, J. S</creatorcontrib><creatorcontrib>HARPER, P. G</creatorcontrib><creatorcontrib>GEDDES, D. M</creatorcontrib><creatorcontrib>ERAUT, D</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>EARL, H. M</au><au>RUDD, R. M</au><au>PARTRIDGE, M. R</au><au>SOUHAMI, R. L</au><au>SPIRO, S. G</au><au>ASH, C. M</au><au>JAMES, L. E</au><au>LAW, C. S</au><au>TOBIAS, J. S</au><au>HARPER, P. G</au><au>GEDDES, D. M</au><au>ERAUT, D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A randomised trial of planned versus as required chemotherapy in small cell lung cancer: a Cancer Research Campaign trial</atitle><jtitle>British journal of cancer</jtitle><addtitle>Br J Cancer</addtitle><date>1991-09-01</date><risdate>1991</risdate><volume>64</volume><issue>3</issue><spage>566</spage><epage>572</epage><pages>566-572</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><coden>BJCAAI</coden><abstract>In a study of chemotherapy as palliative treatment, 300 patients with untreated limited and extensive stage small cell lung cancer (SCLC), who did not have progressive disease after the first cycle of chemotherapy, were randomised to receive either regular 'planned' chemotherapy or chemotherapy given 'as required' (AR). All patients received the same chemotherapy: cyclophosphamide 1 gm m-2 i.v., vincristine 2 mg i.v., and etoposide 120 mg m-2 i.v. on day 1, and etoposide 100 mg b.d. orally on days 2 and 3. Planned chemotherapy was given regularly every 3 weeks. AR chemotherapy was given for tumour-related symptoms, or for radiological progression of disease. Both groups of patients were assessed every 3 weeks and a maximum of eight cycles of chemotherapy was given. A detailed quality of life assessment was made using daily diary cards. The median survival (MS) of patients given AR chemotherapy was not significantly worse than those receiving planned treatment [MS: Planned = 36 weeks (95% C.I. 32-40 weeks), AR = 32 weeks (95% C.I. 28-37 weeks) P = 0.960]. In the AR patients the median interval between treatments was 42 days. On average AR patients received half as much chemotherapy as planned patients. AR patients with a treatment-free interval (TFI) of more than 8 weeks between the first and second cycles of chemotherapy survived longer than those in whom this interval was less than 4 weeks; [MS: TFI greater than 8 = 47 weeks (95% C.I. 32-53 weeks); TFI less than 4 = 24 weeks (95% C.I. 17-34 weeks) P = 0.013]. Contrary to expectation, in the quality of life assessment the AR patients scored themselves as having more severe symptoms than patients receiving planned treatment. AR chemotherapy is a novel method of attempting to use cytotoxic drugs palliatively, which resulted in less drug treatment for approximately equivalent survival. However the palliative effect seen with as required treatment was less satisfactory than with planned chemotherapy.</abstract><cop>Basingstoke</cop><pub>Nature Publishing Group</pub><pmid>1654983</pmid><doi>10.1038/bjc.1991.351</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0007-0920
ispartof British journal of cancer, 1991-09, Vol.64 (3), p.566-572
issn 0007-0920
1532-1827
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1977632
source PubMed Central Free
subjects Aged
Antineoplastic agents
Antineoplastic Combined Chemotherapy Protocols - administration & dosage
Antineoplastic Combined Chemotherapy Protocols - adverse effects
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biological and medical sciences
Carcinoma, Small Cell - drug therapy
Carcinoma, Small Cell - pathology
Chemotherapy
Cyclophosphamide - administration & dosage
Drug Administration Schedule
Etoposide - administration & dosage
Female
Humans
Lung Neoplasms - drug therapy
Lung Neoplasms - pathology
Male
Medical sciences
Middle Aged
Neoplasm Staging
Pharmacology. Drug treatments
Quality of Life
Vincristine - administration & dosage
title A randomised trial of planned versus as required chemotherapy in small cell lung cancer: a Cancer Research Campaign trial
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-03T07%3A14%3A17IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20randomised%20trial%20of%20planned%20versus%20as%20required%20chemotherapy%20in%20small%20cell%20lung%20cancer:%20a%20Cancer%20Research%20Campaign%20trial&rft.jtitle=British%20journal%20of%20cancer&rft.au=EARL,%20H.%20M&rft.date=1991-09-01&rft.volume=64&rft.issue=3&rft.spage=566&rft.epage=572&rft.pages=566-572&rft.issn=0007-0920&rft.eissn=1532-1827&rft.coden=BJCAAI&rft_id=info:doi/10.1038/bjc.1991.351&rft_dat=%3Cpubmed_cross%3E1654983%3C/pubmed_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c433t-250f8c85dc2b50164c4636410e39cccb6eb4f14baf1b52edff40afa4f010cf643%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_id=info:pmid/1654983&rfr_iscdi=true