See also my book under the same name above.
Clinical Oncology (2004) 16: 549e560 doi:10.1016/j.clon.2004.06.007
The Contribution of Cytotoxic Chemotherapy to 5-year Survival in Adult Malignancies
Graeme Morgan*, Robyn Wardy, Michael Bartonz
*Department of Radiation Oncology, Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, NSW; yDepartment of Medical Oncology,
St Vincent’s Hospital, Sydney, NSW; zCollaboration for Cancer
Outcomes Research and Evaluation, Liverpool Health Service, Sydney, NSW, Australia
Aims: The debate on the funding and availability of cytotoxic drugs raises questions about the contribution of curative or adjuvant cytotoxic chemotherapy to survival in adult cancer patients.
Materials and methods: We undertook a literature search for randomised clinical trials reporting a 5-year survival beneﬁt attributable solely to cytotoxic chemotherapy in adult malignancies. The total number of newly diagnosed cancer patients for 22 major adult malignancies was determined from cancer registry data in Australia and from the Surveillance Epidemiology and End Results data in the USA for 1998. For each malignancy, the absolute number to beneﬁt was the product of (a) the total number of persons with that malignancy; (b) the proportion or subgroup(s) of that malignancy showing a beneﬁt; and (c) the percentage increase in 5-year survival due solely to cytotoxic chemotherapy. The overall contribution was the sum total of the absolute numbers showing a 5-year survival beneﬁt expressed as a percentage of the total number for the 22 malignancies.
Results: The overall contribution of curative and adjuvant cytotoxic chemotherapy to 5-year survival in adults was estimated to be 2.3% in Australia and 2.1% in the USA.
Conclusion: As the 5-year relative survival rate for cancer in Australia is now over 60%, it is clear that cytotoxic chemotherapy only makes a minor contribution to cancer survival. To justify the continued funding and availability of drugs used in cytotoxic chemotherapy, a rigorous evaluation of the cost-eﬀectiveness and impact on quality of life is urgently required. Morgan, G. et al. (2004). Clinical Oncology 16, 549e560
© 2004 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Key words: Chemotherapy, combined modality treatment, palliation, quality of life, radiotherapy, survival
Received: 18 August 2003 Revised: 20 April 2004 Accepted: 3 June 2004
In adults, cytotoxic chemotherapy became established in the 1970s as a curative treatment in advanced Hodgkin’s disease , non-Hodgkin’s lymphoma , teratoma of testis  and as an adjuvant treatment for early breast cancer .
The initial results suggested the potential use of cytotoxic chemotherapy as a deﬁnitive treatment or as an adjuvant therapy in asymptomatic patients with the aim of improving survival. However, as stated by Braverman  and others
[6e8], the early gains in a few tumour sites have not been seen in the more common cancers. For most patients, the use
of cytotoxic chemotherapy is for the palliation of symptoms and to improve quality of life , with prolongation of survival being a less important outcome.
Author for correspondence: Dr Graeme W. Morgan, Director, Radiation Oncology, Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney NSW 2065, Australia. Tel: D61-2-9926-5010; Fax: D61-2-9906-
- E-mail: firstname.lastname@example.org
Some practitioners still remain optimistic that cytotoxic chemotherapy will signiﬁcantly improve cancer survival . However, despite the use of new and expensive single and combination drugs to improve response rates and other agents to allow for dose escalation, there has been no change in some of the regimens used, and there has been little impact from the use of newer regimens. Examples are non-Hodgkin’s lymphoma  and ovarian cancer , in which cyclophosphamide, adriamycin, vincristine and prednisolone (CHOP) and platinum, respectively, (intro- duced over 20 years ago) are still the ‘gold standard’ treatment. Similarly, in lung cancer, the median survival has increased by only 2 months during the same time period [13,14], and an overall survival beneﬁt of less than 5% has been achieved in the adjuvant treatment of breast, colon,
and head and neck cancers [15e17].
The recent debate on funding of new cytotoxic drugs [18e20] has highlighted the lack of agreement between medical oncologists and funding bodies on the current and
0936-6555/04/080549C12 $35.00/0 © 2004 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
future value of cytotoxic chemotherapy in cancer manage- ment.
In 1986, Kearsley  estimated that the contribution of chemotherapy to overall survival in the USA was 4.3%. By reassessing the contribution of deﬁnitive and adjuvant cytotoxic chemotherapy to 5-year survival in adult malig- nancies, we sought to update the estimate in order to provide a more rational basis for the current debate on funding and availability
We undertook a literature search for randomised-controlled trials (RCTs) that reported a statistically signiﬁcant in- crease in 5-year survival due solely to cytotoxic chemo- therapy in adult malignancies (deﬁned as 20 years of age or over). The search period was from 1 January 1990 until 1 January 2004. We searched Medline, Cancerlit and Embase to identify RCTs for each neoplasm using the MeSH headings of chemotherapy, radiotherapy and combined modality treatment. We used the Cochrane Collaboration and the Cochrane Cancer Library to identify meta-analyses and systematic reviews reporting the pooled results of RCTs. We also hand searched reference lists in published papers and other relevant articles.
We accepted the results of the RCTs, meta-analyses or systematic reviews as reported, and did not critically review the data further. As a measure of long-term survival and possible cure, 5-year survival data were used. When 5-year data were not available, shorter survival times were used, provided the outcome reported was statistically signiﬁcant. We did not attempt to evaluate the eﬀect on cancer outcomes of hormones, immunotherapy, antibodies, tumour vaccines, gene therapy or other novel techniques. Similarly, we did not evaluate the use of cytotoxic chemotherapy for the palliation or non-curative treatment of malignancy, as an impact on 5-year survival was unlikely.
The preferred source of evidence was either a systematic review or a meta-analysis of the RCTs for that malignancy. An RCT could take precedence over a systematic review or meta-analysis, but only when the RCT was from a reputable trials group, more recent than the systematic review or meta-analysis, randomised approximately 1000 patients, and the results were of such a magnitude that data from a previous analysis was clearly inferior.
For each malignancy, the absolute number of individuals obtaining an improvement in 5-year survival as a result of chemotherapy was the product of the number of newly diagnosed cancer patients aged over 20 years with that malignancy, the proportion or subgroup(s) showing a ben- eﬁt, and the percentage increase in 5-year survival resulting solely from cytotoxic chemotherapy.
For the 22 major malignancies evaluated (Tables 1 and 2), the number of individuals with cancer aged 20 years and over in 1998 were calculated, using the cancer incidence data for Australia from the Australian Institute of Health and Welfare (AIHW)  (http://www.aihw.gov.au) and
the Surveillance, Epidemiology, and End Results (SEER) data for the USA  for 1998.
Malignancies with small total numbers, such as gall bladder, pleura, eye, bone, penis and placenta were excluded. Acute and chronic leukaemia (n ¼ 1647 or 2% of total) were not included because of the diﬃcultly in de-
ﬁning outcomes according to FAB (FrencheAmericane British) classiﬁcation and the diﬀerent outcomes for children and adults. Also, these patients are usually cared
for by clinical haematologists rather than medical oncol- ogists. For Australia, the 22 malignancies evaluated were 90% of the total number of newly diagnosed cancer patients for 1998.
In most instances, the contribution to 5-year survival applied to subgroups that varied according to histology, stage, nodal involvement or menopausal status. The size of these subgroups was obtained from data on the distribution of stage in the South Australian Cancer Registry for 1998 , from the SEER data for 1998  or from patterns of care studies .
The percentage increase in 5-year survival with cytotoxic chemotherapy for the malignancy as a whole or for the subgroup was identiﬁed by the literature search as detailed above. Each malignancy was evaluated separately and the absolute number of people to beneﬁt was established. The overall contribution of cytotoxic chemotherapy to 5-year survival was the sum total of the absolute numbers to beneﬁt expressed as a percentage of the total number of cancer patients in the 22 malignancies evaluated.
To establish the general applicability of the data, the contribution to 5-year survival was calculated separately for Australia and the USA. Where assumptions were made, we erred on the side of over-estimating the beneﬁt.
Results are arranged in ICD-9 groupings and are presented in Tables 1 and 2.
Head and Neck Cancer
ICD-9: 140e149, 160, 161; incidence: 2486 (Australia),
Most people with head and neck cancer are treated for cure with radical surgery, radiotherapy, or a combination of both. Three meta-analyses were identiﬁed [25e27], which did not show any beneﬁt from adding chemotherapy to
radical radiotherapy with or without surgery. A subgroup analysis of a more recent meta-analysis showed a 4% overall improvement in survival with concurrent radiother- apy and chemotherapy . The improvement was re- stricted to people with extensive disease, and this has been shown separately in advanced glottic cancer  and cancer of nasopharynx . The beneﬁt from chemother- apy will only be seen for those with stage III and IV disease. In 1998, this was 63% of the total in Australia and 47% of the total in the USA.
Table 1 e Impact of cytotoxic chemotherapy on 5-year survival in Australian adults
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