chemotherapy-induced bowel obstruction in small cell lung cancer: a case report

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Medical Oncology

ISSN 1357-0560

Med Oncol

DOI 10.1007/s12032-011-0150-3

Chemotherapy-induced bowel obstructionin small cell lung cancer: a case report

Jermaine I. G. Coward, Nicola-Louise

Ding, Roger Feakins, Hermant Kocher,

Sanjay Popat & Piotr W. Szlosarek



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S H O R T C O M M U N I C A T I O N

Chemotherapy-induced bowel obstruction in small cell lungcancer: a case report

Jermaine I. G. Coward • Nicola-Louise Ding •

Roger Feakins • Hermant Kocher • Sanjay Popat •

Piotr W. Szlosarek

Received: 13 December 2011/ Accepted: 20 December 2011

Springer Science+Business Media, LLC 2011

Abstract This case report focuses on an elderly gentleman

with extensive stage small cell lung cancer (SCLC) whoexperienced episodes of bowel obstruction shortly after

commencing first-line chemotherapy with cisplatin and eto-

poside. The patient had no radiological or pathological evi-

dence of intra-abdominal carcinomatosis or paraneoplastic

bowel disease secondary to SCLC. Although neurotoxicity is

commonly associated with platinum agents, the effect is

predominantly peripheral as opposed to autonomic. The

authors conclude that the observations documented in this

case were secondary to etoposide; a podophyllotoxin that can

bind microtubules and inhibit fast axonal transport. Although

paralytic ileus is well recognised with podophyllotoxin poi-

soning, to our knowledge, this is the first report to associate

bowel obstruction with standard doses of etoposide and

highlights the need for physicians to be aware of such dele-

terious effects in patients treated with this cytotoxic agent.

Keywords Small cell lung cancer Bowel obstruction

Etoposide

Podophyllotoxin

Neurotoxicity

Paraneoplastic AXR

Introduction

The treatment of small cell lung cancer (SCLC) with plati-

num-based chemotherapy still remains the standard of first-

line care, with a doublet containing the podophyllotoxin,

etoposide, being the most widely adopted regime [1]. SCLC

is often associated with a spectrum of paraneoplastic con-

ditions that can manifest as aberrant hormone secretion (e.g.

vasopressin (ADH) and adrenocorticotrophic hormone (AC

TH)), neurological syndromes (Lambert-Eaton syndrome)

or intestinal pseudo-obstruction. The inherent chemosensi-

tivity of SCLC is exemplified by the fact that these presen-

tations can respond in up to 80% of cases treated with

platinum-etoposide in the first instance [2]. Despite this,

most patients succumb within either 15–20 months for

limited stage or 8–13 months for extensive stage disease

[2–4]. This case report documents the observation of bowel

obstruction induced by carboplatin and etoposide in a patient

with extensive stage SCLC.

Case history

In December 2005, a 62-year-old gentleman with an 80-pack

year smoking history was diagnosed with extensive stage

small cell lung cancer by transbronchial biopsy following an

acute presentation of dyspnoea. Baseline computer tomog-

raphy (CT) staging revealed a left hilar mass arisingfrom the

lower lobe bronchus associated with pretracheal and

J. I. G. Coward (&) S. Popat

Royal Marsden Hospital NHS Foundation Trust, Fulham Road,

London SW3 6JJ, UK

e-mail: [email protected]

J. I. G. Coward H. Kocher P. W. Szlosarek

Barts Cancer Institute, Queen Mary University of London,

Charterhouse Square, London EC1M 6BQ, UK

N.-L. Ding H. Kocher P. W. Szlosarek

St Bartholomew’s Hospital, West Smithfield,

London EC1A 7BE, UK

R. Feakins

The Royal London Hospital, 80 Newark Street, Whitechapel,

London E1 2ES, UK

S. Popat

Molecular Genetics Group, Imperial College London,

Dovehouse Street, London, UK

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Med Oncol

DOI 10.1007/s12032-011-0150-3



subcarinal lymphadenopathy. There was no evidence of any

extrathoracic visceral metastases. Within a few days of diagnosis, the patient commenced chemotherapy with car-

boplatin AUC 5 i.v. day 1 and etoposide 200 mg/m2 i.v. day

1 and 100 mg/m2 p.o. b.d. day 2 and 3. On day 8, sudden

onset left upper quadrant pain ensued which was associated

with vomiting. Although generalised abdominal tenderness

was elicited on palpation, bowel sounds were normal in

character, and no guarding was evident. A subsequent

abdominal X-ray (AXR) confirmed faecal loading in the

ascending colon in addition to gas in the rectosigmoid and

proximal bowel loop. CT imaging had indicated some

interval response in the left hemithorax disease, but there

were no significant findings within the abdomen. Althoughsymptoms initially settled with analgesia, after a further

week, increasing abdominal distension and tenderness

developed. A repeat AXR (Fig. 1a) and CT scan revealed

small bowel obstruction, and a subsequent laparotomy

involved excision of the parietal omentum with two small

bowel resections and side-to-side anastomosis, with no

suspicion of peritoneal metastases. The post-operative AXR

is shown in Fig. 1b.

Pathology review of the resected bowel specimen and

omentum demonstrated areas of ulceration and oedema.

Histology showed severe ulceration and transmural necrosis

with haemorrhage and quite extensive fibrosis (Fig. 2).A few submucosal and subserosal blood vessels contained

organised thrombi, and there was no evidence of, inflam-

matory bowel disease or neoplasia or any neuronal degen-

eration suggestive of paraneoplastic phenomenon.

In February 2006, the second cycle of chemotherapy

commenced. However, on day 3, the patient experienced

severe sudden onset lower abdominal pain, associated with

vomiting. The abdominal symptoms deteriorated rapidly with

guarding and absent bowel sounds associated with oliguria

and hypotension. The AXR (Fig. 1c) and CT scan showed

evidence of dilated small bowel and an abdominal purulent

collection that was subsequently drained. Furthermore,

despite evidence of an interval response after the first cycle of

chemotherapy, disease progression was confirmed within the

thorax. After 1 week of conservative treatment, the clinical

state improved and his stablecondition facilitatedtransfer to ahospice. In view of the poor performance status and rapid

disease progression on platinum-based treatment, second-line

therapy was not considered.

Discussion

This case highlights recurrent unexpected toxicities sec-

ondary to carboplatin and etoposide treatment in a patient

Fig. 1 Abdominal X-rays illustrating the development of small bowel obstruction shortly after first exposure to carboplatin and etoposide (a),

that resolved with surgical management (b). Following re-exposure to carboplatin and etoposide, gross small bowel dilatation recurred (c)

Fig. 2 Small bowel showing ulceration with loss of full thickness of

the mucosa (top half of picture) and underlying granulation tissue

formation and fibrosis. Viable but inflamed mucosa is present in the

lower half of the picture. There is no evidence of neoplasia

Med Oncol

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with no pre-existing bowel co-morbidity, evidence of

intestinal paraneoplastic syndrome secondary to SCLC, or

abdominal metastases by CT. Although platinum agents are

associated with neurotoxicity, due to the predominant

effect on large myelinated nerves, the neuropathy usually

manifests in the peripheral as opposed to autonomic ner-

vous system [5]. Etoposide has dual chemotherapeutic

properties in that it is a synthetic podophyllotoxin deriva-tive that also behaves as a topoisomerase II inhibitor that

results in S-phase/early G2 cell cycle growth arrest and the

maintenance of torsional stresses in DNA that inhibit

strand breakage. However, the podophyllotoxic effect of

etoposide relates to microtubular binding and inhibition of

fast axonoplastic transport [6, 7]. In view of the autonomic

bowel dysfunction commonly associated with other

microtubular toxins such as vinca alkaloids, it is feasible

that the symptoms outlined in this report were attributable

to etoposide. Nevertheless, this is a symptom that has only

been rarely reported, and in one such case etoposide was

administered with amsacrine, another topoisomerase IIinhibitor [8]. Furthermore, although podophyllotoxin poi-

soning is certainly associated with paralytic ileus [9, 10], to

our knowledge, this is the first report of bowel obstruction

secondary to etoposide given as a standard dose in the

absence of other expected toxicities. Conversely, intra-

peritoneal etoposide has been shown to relieve symptoms

secondary to abdominal carcinomatosis in metastatic lung

adenocarcinoma that was refractory to treatment with

chemo-immunotherapy [11]. Hence, the observations pre-

viously described in this report appear to be paradoxical.

Whilst we cannot completely exclude intra-abdominal

metastases that might have been apparent on PET-CT in

our case, no evidence of intra-abdominal tumour was evi-

dent at laparotomy.

Similar to many other cytotoxic agents, intestinal

mucositis is associated with etoposide and is depicted by

villous atrophy, significant crypt disruption and lymphoid

cell infiltrates [12]. In addition, a recent report has shown

that such bowel injury is preceded by endothelial damage

[13]. The events observed in this report emphasise the need

for physicians to be aware of additional bowel toxicities

that are associated with etoposide-based regimens.

Acknowledgments JC and SP acknowledge NHS funding to theNIHR Biomedical Research Centre. SP is in receipt of a Clinical

Senior Lecturer Award from the Higher Education Funding Council

for England. PWS is in receipt of a Clinician Scientist fellowship

from Cancer Research UK.

Conflict of interest None.

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Med Oncol

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chemotherapy-induced bowel obstruction in small cell lung cancer: a case report

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