The problem of marrow suppression is inevitable with aggressive chemotherapy, although the severity varies. The possibility of using granulocyte colony stimulating factor (G-CSF) to improve marrow function during chemotherapy has been explored [14]. In one study, 403 patients were treated with ACE (doxorubicin, cyclophosphamide and etoposide) given 3 weekly in the control group but every 2 weeks with additional G-CSF in the experimental group. Complete response and survival were improved in the intense treatment group, and quality of life was no worse. The benefit of maintaining the hemoglobin level in patients undergoing chemotherapy for small cell cancer has also been studied. Seventy-four patients with small cell cancer received combination chemotherapy with carboplatin and etoposide with or without additional darbepoetin, an erythropoiesis stimulating agent [15]. The aim in the intervention group was to maintain a hemoglobin of 12–13 g/dL. Whilst darbepoetin reduced the need for blood transfusion and improved some elements of the EORTC (European Organisation for Research and Treatment of Cancer) quality of life questionnaire, it did not produce a global improvement. Both erythropoiesis and granulocyte stimulating agents are expensive and this approach has not been subject to cost-effectiveness analysis. They are not used routinely in the UK.

Although chemotherapy agents can induce a range of adverse effects, this has to be set against their potential for shrinking or even curing the cancer, and thereby improving the symptoms produced by the malignant disease itself. Even in patients with relatively good performance status and prognosis, baseline symptoms are common. Thatcher and colleagues reported a cohort of 402 patients who were treated with standard chemotherapy regimens (ACE or carboplatin-etoposide) or with more aggressive ICE-V (ifosfamide, carboplatin, etoposide, and vincristine) [16]. At baseline about one-quarter reported their overall quality of life as poor or extremely poor. Chemotherapy produced improvements in both groups. For ICE-V the percentage with poor or extremely poor quality of life fell from 25 to 13 % at 3 months, and to 14 % at 6 months, while for the standard regime the equivalent figures were 24, 16, and 15 %. Moreover, many specific symptoms such as cough, dyspnea, and appetite improved after chemotherapy was started, although others such as general fatigue and levels of energy did not.

In a later study, Quoix measured quality of life using the functional assessment of cancer therapy-lung questionnaire (FACT-L), and also looked at individual symptoms. This was linked to a comparison of topotecan used with either cisplatin or etoposide. There was no difference in outcome between the two treatment groups, but it was noteworthy that all baseline symptoms improved with both treatment combinations, with the exception of hemoptysis [17].

The balance between prolongation of life and changes in the quality of life is perhaps most important in those patients with poor prognosis. Frustratingly there remains a paucity of good information on quality of life changes with chemotherapy in this group. A Cochrane review found only two studies of first line chemotherapy versus best supportive care in extensive stage small cell lung cancer, comprising a total of 65 patients [18]. The review concluded that the impact of chemotherapy on quality of life in poor prognosis small cell cancer is uncertain. In addition, a large study in which patients with small cell cancer of various stages were randomized to receive either paclitaxel, carboplatin, and etoposide, or vincristine, carboplatin, and etoposide, reported the results separately for the stage four patients [19]. The global quality of life parameters of the EORTC questionnaire improved. However, it is important to note that in this study patients were well enough to be randomized to receive potentially toxic systemic chemotherapy, and thus are not truly representative of the generality of patients with extensive stage disease. It remains the case that the patients with most symptoms (i.e., who have most to gain from treatment) are also those least likely to be able to tolerate chemotherapy.

An unpleasant persistent cough is a common problem in advanced lung cancer particularly with more central lesions as cough receptors are present in greater density in central airways. Radiotherapy is a potential treatment option, the benefit presumably relating to shrinkage of the tumor. The success rate for significant palliation of cough is a little over 50 %, although this estimate is based on retrospective review [32]. One prospective evaluation using a standardized questionnaire found a disappointing response rate of 31 % [29]. The technique of endobronchial radiotherapy (brachytherapy) has been described in Chap.3. It is probably inferior to external beam radiotherapy for palliation of symptoms, but has the advantage of being potentially applicable in patients who have already had maximal dose of conventional radiotherapy, the limiting factor being that the lesion has to be accessible to the bronchoscope in order to position the treatment catheters. Brachytherapy has been used to treat patients with symptomatic tumor recurrence after primary treatment with high-dose radiotherapy and a ­surprisingly good response rate of 77 % was seen for improvement of cough [33].

As with cough, hemoptysis secondary to lung cancer has long been treated with radiotherapy, and brachytherapy is again an option in those patients who have already received external beam therapy. Hemoptysis seems to respond well to radiotherapy. A prospective study using a validating questionnaire showed that the symptom disappeared or improved significantly in 83 % of patients [29]. In a separate retrospective study, the response to brachytherapy as second line treatment of hemoptysis was 92 % [33].

Breathlessness can arise for several different reasons in lung cancer. When it is caused by the development of a pleural or pericardial effusion, or by anemia, radiotherapy has no role, nor is it of any benefit when dyspnea is caused by lymphangitis carcinomatosa. However, when breathlessness has arisen because of mechanical obstruction of a large bronchus, with or without collapse of the distal lung, radiotherapy may be of value in shrinking the tumor and relieving the obstruction. Unfortunately, even if the tumor responds, re-expansion of collapsed lung is not guaranteed. Experience suggests that expansion is less likely the longer the lung remains in its non-aerated state, and treatment of dyspnea due to obstruction of tumor should consider the role of radiotherapy in conjunction with other treatment such as stents or laser therapy. Because tumor response in this situation does not necessarily lead to lung re-expansion, the response rates for breathlessness treated by radiotherapy tend to be poorer than those for symptoms such as hemoptysis. In a prospective study, the response rate for dyspnea was 37 % [29].

Lung cancer can produce pain by local invasion of the chest wall or through distant metastases, particularly to bone. The degree of discomfort and the likelihood of a worthwhile response to radiotherapy differ a little with the extent of the invasion, but some relief is usually achieved. A response rate of 68 % has been found in a prospective study [29]. For distant bone metastases, studies have shown that a single fraction of 8 Gy is as effective as higher dose multi-fraction therapy in relieving pain [34]. Response to radiotherapy is usually reasonably quick and treatment need not be withheld because a patient is judged to be within a few weeks of death – improvement of pain at 1 month is found in 70 % of patients [35]. Treatment of bone metastases can be associated with further weakening of the bone, and this is particularly important in weight-bearing sites, such as the femur. Adequate palliation should involve orthopaedic advice, and it may be necessary for patients to avoid weight bearing for a period of time or to undergo a surgical stabilization procedure.

The brain is a relatively common site of metastases for both small cell and non-small cell cancer. In the latter case, the metastasis may be solitary and in that situation treatment via surgery or stereotactic radiotherapy with a view to cure may occasionally be appropriate.