Performance status (PS) and the physiologic status of the patient should guide treatment decision rather than the patient’s chronologic age. It is clear that elderly patients with good PS (ECOG 0 or 1) and normal organ function should be treated with optimal chemotherapy (and radiotherapy if indicated) as in their younger counterparts. Similar outcomes for elderly patients (in comparison to their younger counterparts) with limited-stage SCLC have been shown in the Intergroup trial 0096 in which cisplatin, etoposide, and thoracic radiotherapy was administered once per day or twice daily. The National Cancer Institute of Canada performed a retrospective review of their BR3 and BR6 trials and also concluded that age did not appear to impact the delivery, tolerance, or efficacy of thoracic irradiation in the combined modality management of limited-stage SCLC. Greater myelosuppression is to be expected because equivalent exposure to drug will lead to more myelosuppression in the elderly. This has been shown to be the case with etoposide. Greater ancillary support therefore will be required in the elderly. However, despite treatment delays, elderly patients with good PS derive the same level of benefit relative to younger patients.
Elderly patients with poor PS or with compromised organ function may be offered single-agent chemotherapy or polychemotherapy in attenuated doses. However, several randomized studies’ have indicated that such “gentler” chemotherapy is inferior to optimal combination chemotherapy. Options available to these patients include oral etoposide for 14 days combined with carboplatin on day 1 every 28 days; abbreviated chemotherapy with CAV in full doses followed up 3 weeks later by cisplatin and etoposide in optimal doses; or chemotherapy with platinum, adriamycin, vincristine, and etoposide, with all four drugs in reduced doses. A phase III trial compared carboplatin/gemcitabine with cisplatin/etoposide in patients with poor-prognosis SCLC, with carbo-platin and gemcitabine exhibiting a more favorable overall toxicity profile at the expense of increased myelotoxicity but with equivalent efficacy. Another phase III trial compared single-agent car-boplatin with CAV, with carboplatin producing response rates, relief of tumor-related symptoms, and survival similar to that seen with CAV. There was a lower risk of life-threatening sepsis and less need for hospitalization in the group that received carboplatin.
Recommendations
Elderly patients with good PS (ECOG PS 0 or 1) with intact organ function should be treated with platinum-based chemotherapy.
Grade of recommendation, 1A
Elderly patients with poor prognostic factors such as poor PS or medically significant concomitant comorbid disease may still be considered for chemotherapy. Grade of recommendation, 2C
Studies with SCLC cell lines have shown that they have greater radiosensitivity than human adenocarcinomas or squamous cell lung cancer cell lines. Because of these observations, many early trials of combining radiation with chemotherapy in SCLC used lower total radiation doses. It has become increasingly clear that higher doses than those of the old regimens of 30 Gy in 10 fractions or 45 Gy in 25 fractions are needed to provide durable local control because lower doses are associated with local relapse rates in excess of 50%. Become healthier with My Canadian Pharmacy’s remedies.
A number of trials conducted in the 1970s and 1980s compared chemotherapy alone to chemotherapy plus TRTx in patients with limited SCLC. There were differences in radiation dose, timing, and choice of chemotherapeutic agents, but most were performed with alkylating agent and doxorubicin-based therapy rather than cisplatin and etoposide. The analysis by Warde and Payne showed improved local control and survival with the addition of TRTx, particularly in patients < 60 years old. Pignon et al obtained individual patient data from these trials and was able to update analyses from the time of original publication. They found that the addition of TRTx resulted in an increase in 3-year survival from 8.9 to 14.3%, an absolute improvement of 5%, and a relative improvement of nearly 50%. With the publication of these two metaanalyses, the debate shifted from whether to use TRTx to how best to integrate it with chemotherapy.
In limited disease, the ability to use concurrent therapy is predicated on avoiding drugs with in-trathoracic organ toxicity that compound with radiotherapy. The optimal chemotherapy to utilize with radiation therapy has been a subject of investigation as well. A prospective randomized trial comparing cisplatin and etoposide (PE) to cyclophosphamide, etoposide and vincristine (CEV) was reported by Sundstrom et al. A total of 436 eligible patients were randomized to chemotherapy with PE (n = 218) or CEV (n = 218). Patients were stratified according to extent of disease (limited disease, n = 214; extensive disease, n = 222). The PE group received five courses of etoposide at 100 mg/m2 IV and cisplatin at 75 mg/m2 IV on day 1, followed up by oral etoposide 200 mg/m2/d on days 2 to 4. The CEV group received five courses of epirubicin at 50 mg/m2, cyclophosphamide at 1,000 mg/m2, and vincristine at 2 mg, all IV, on day 1. In addition, patients with limited disease received TRTx concurrent with chemotherapy cycle 3, and those achieving CR during the treatment period received PCI. The 2-year and 5-year survival rates in the PE arm (14% and 5%; p = 0.0004) were significantly higher compared with those in the CEV arm (6% and 2%). Among patients with limited disease, median survival time was 14.5 months vs 9.7 months in the PE and CEV arms, respectively (p = 0.001). The 2-year and 5-year survival rates of 25% and 10% in the PE arm compared with 8% and 3% in the CEV arm (p = 0.0001). Quality-of-life assessments revealed no major differences between the randomized groups. The authors concluded that PE is superior to CEV in patients with limited-disease SCLC. Therefore, PE is the recommended chemotherapy regimen to combine with TRTx in the treatment of limited-stage SCLC.
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