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Treatment of refractory and relapsed small cell lung cancer

Treatment of refractory and relapsed small cell lung cancer
Literature review current through: May 2024.
This topic last updated: May 30, 2024.

INTRODUCTION — Small cell lung cancer (SCLC) represents 15 percent of all lung cancers and occurs almost exclusively in smokers. It is distinguished from non-small cell lung cancer by its rapid doubling time, high growth fraction, and the early development of widespread metastases. Although considered highly responsive to chemotherapy and radiotherapy, SCLC usually recurs within 14 to 15 months for patients with limited-stage SCLC and five to six months for patients with extensive-stage SCLC. Many of these patients are candidates for additional systemic treatment.

The median survival of patients with relapsed SCLC ranges from two to six months. The most important factors affecting prognosis are performance status, tumor extent (ie, limited versus extensive), and time to relapse after first-line therapy [1]. For refractory disease (no initial response) or resistant relapse (disease-free interval less than three months from the last day of initial treatment), most agents or regimens demonstrate low response rates (<10 percent). However, for sensitive relapse (time to relapse greater than three months from the last day of initial treatment), the response rate is approximately 25 percent [2].

Similarly, the likelihood of an objective response to second-line therapy depends upon the time from last therapy to relapse, the response to initial treatment, and the performance status.

The treatment of relapsed and refractory SCLC will be reviewed here. The initial management of SCLC and experimental approaches to treatment are considered separately. (See "Extensive-stage small cell lung cancer: Initial management" and "Limited-stage small cell lung cancer: Initial management".)

DEFINITIONS OF REFRACTORY DISEASE AND SENSITIVE VERSUS RESISTANT RELAPSE — The length of response to initial treatment influences the likelihood of response to subsequent treatment. If the disease free-interval was less than three months from the last day of initial treatment (resistant relapse) or there was no initial response (refractory disease), most agents or regimens demonstrate low response rates (<10 percent). However, if the time to relapse was greater than three months from the last day of initial treatment (sensitive relapse), the response rate is approximately 25 percent [2].

PATIENTS WITH RELAPSE WITHIN 6 MONTHS OF TREATMENT

Approach — The approach below applies to patients with primary refractory disease and resistant relapse, as well as patients with sensitive relapse >90 days to 6 months, since treatment approaches are the same.

Single-agent chemotherapy is standard second-line treatment after platinum-based chemotherapy and immunotherapy. Lurbinectedin represents our preferred initial approach, although camptothecins are also acceptable. In choosing between lurbinectedin and camptothecin, lurbinectedin is associated with a milder toxicity profile, although it may not yet be widely available. (See 'Lurbinectedin' below and 'Camptothecins, as an alternative' below.)

For those who cannot tolerate or progress on these agents, tarlatamab is an alternative or later-line option, with regulatory approval. (See 'Tarlatamab' below.)

For patients that are not eligible for, cannot tolerate, or progress on tarlatamab, other chemotherapy agents are available. (See 'Later-line options' below.)

The data below represent efficacy of chemotherapy after progression on initial combination chemotherapy. These trials were conducted prior to introduction of immunotherapy into the management of SCLC.

Preferred, if available

Lurbinectedin — Lurbinectedin is an alkylating agent that has received accelerated approval by the US Food and Drug Administration (FDA) for patients with metastatic SCLC with disease progression on or after platinum-based chemotherapy [3]. It is given at a dose of 3.2 mg/m2 intravenously (IV) every three weeks.

In an open-label study of 105 patients with SCLC and no brain metastases who progressed on or after platinum-based chemotherapy, 8 percent of whom had prior immunotherapy in addition to platinum-based chemotherapy, the overall response rate (ORR) with lurbinectedin according to independent review committee was 33 percent [3,4]. The median duration of response was 5.1 months, and 25 percent of responding patients experienced a duration of response exceeding six months. Among patients with resistant relapse (chemotherapy-free interval <90 days), the ORR was 22 percent with a progression-free survival (PFS) of 2.6 months and an overall survival (OS) of 5 months. For patients with sensitive relapse, the ORR was 45 percent with a PFS of 4.5 months and an OS of 11.9 months [4].

All patients in this study received a prespecified antiemetic regimen consisting of a corticosteroid and serotonin antagonist. Serious adverse reactions occurred in 10 percent of patients, of which neutropenia and febrile neutropenia were the most common (5 percent for each).

Camptothecins, as an alternative

Topotecan

Efficacy and toxicity — Topotecan has been shown to increase survival compared with best supportive care (BSC) and results in greater symptom management relative to a multiagent regimen [5,6]. It is approved by the FDA for relapses that occur after 45 days from the completion of chemotherapy. Topotecan also has activity against brain metastases. The primary toxicities of topotecan are hematologic, with most patients experiencing grade 3 or 4 neutropenia, anemia, or thrombocytopenia.

In a trial in which 211 patients with relapse ≥60 days after completion of first-line therapy (usually platinum plus etoposide) were randomly assigned to daily IV topotecan or cyclophosphamide, doxorubicin, and vincristine (CAV), disease outcomes were similar between the groups, but cancer symptoms were improved with topotecan [6]. For topotecan versus CAV, the ORRs were 24 versus 18 percent, the median time to progression was 13 versus 12 weeks, and the median survival was 25 versus 24.7 weeks, differences that were not statistically significant. Control of several symptoms including dyspnea, anorexia, hoarseness, and fatigue was improved with topotecan. Severe neutropenia was less common with topotecan (38 versus 51 percent), but grade 3 or 4 thrombocytopenia and anemia occurred more frequently (9.8 versus 1.4 percent and 17.7 versus 7.2 percent, respectively). The improvement in symptom control led to its FDA approval.

In a trial of 141 patients with sensitive or resistant relapse randomly assigned to oral topotecan (2.3 mg/m2 daily for five days every three weeks) or BSC, topotecan was associated with improved OS (26 versus 14 weeks) [5]. Among the 41 patients with relapse within 90 days, topotecan was associated with a response rate of 10 percent and a clinical benefit rate (responding disease plus stable disease) of 52 percent. The response rate for the 30 patients with sensitive relapse (>90 days) was 3 percent, and the clinical benefit rate in this subset was 50 percent. Patients on topotecan also experienced slower quality of life deterioration and improved symptom control. Principal toxicities with topotecan were hematologic: grade 4 neutropenia, 33 percent; grade 4 thrombocytopenia, 7 percent; and grade 3/4 anemia, 25 percent. Toxic deaths occurred in four patients (6 percent) in the topotecan arm.

The oral and IV formulations of topotecan appear to have similar efficacy. (See 'Dosing and formulation' below.)

The utility of topotecan for relapsed SCLC is not dependent upon age. In a retrospective analysis of four observational studies and a randomized trial, there were 161 patients ≥65 years and 319 <65 years [7]. The objective response rate (including both sensitive and resistant relapse) was the same in the two groups (14 versus 15 percent). The incidence, severity, and duration of grade 4 hematologic toxicities were also similar (in patients ≥65 years versus <65 years, anemia: 4 versus 3 percent, neutropenia: 77 versus 72 percent, and thrombocytopenia: 35 versus 24 percent).

Dosing and formulation

Formulation – Oral and IV formulations of topotecan have been extensively evaluated for the second-line treatment of relapsed SCLC and are found to be equally effective [5,6,8,9].

In a phase III noninferiority trial, 304 patients with chemosensitive relapse (>90 days) of SCLC were randomly assigned to oral (2.3 mg/m2 daily for five days) or IV (1.5 mg/m2 daily for five days) topotecan every three weeks. Response rates were similar (18 versus 22 percent), as were median and one-year survival rates (33 versus 35 weeks and 33 versus 29 percent, respectively) [9]. The toxicity profiles of the two regimens were similar as well.

Schedule of topotecan administration – We prefer giving topotecan daily times five every three weeks rather than a once-weekly schedule, given better efficacy in cross-trial comparisons. In the S0802 phase II trial, 192 patients with previously treated SCLC were randomly assigned to weekly topotecan with or without aflibercept after progression on a platinum-based regimen [10]. Only two partial responses (1 percent) were observed in the entire study population (both in patients who also received aflibercept), and the median OS was approximately five months. Response rates of the daily times five every three weeks schedule were higher in other studies, on the order of 20 percent [6,8,9]. These data are discussed above.

Weekly administration has also shown low efficacy in other disease settings; topotecan on a weekly schedule in ovarian cancer appears to be less effective than the daily schedule in that setting [11].

Irinotecan — As an alternative to topotecan, three small clinical trials have evaluated irinotecan as second-line therapy, with objective response rates ranging from 16 to 47 percent [12-14]. As an example, in one study, 44 patients (17 with sensitive relapse and 27 with resistant or refractory disease) were treated with irinotecan 125 mg/m2 weekly times four with a two-week break [14]. The overall objective response rate was 16 percent. The response rate in patients with resistant or refractory disease was 4 percent. The response rate was 35 percent in the patients with sensitive relapse, with a median survival of 6.8 months. Primary toxicities of irinotecan included diarrhea and neutropenia. Results for those with sensitive relapse are discussed below.

PATIENTS WITH RELAPSES >6 MONTHS AFTER TREATMENT (LATE RELAPSE) — For patients with late relapses (at least six months after completion of chemotherapy), who are on maintenance immunotherapy, there are no data regarding reintroduction of chemotherapy. However, we use this approach, given that chemotherapy is the backbone of all treatment for SCLC and has demonstrated benefit in patients receiving a platinum doublet. Some UpToDate contributors do not continue maintenance immunotherapy for these patients, given toxicity concerns, but there are no data for or against continuation of immunotherapy in this setting.

For patients who did not receive immunotherapy, we offer reinduction with the original platinum-based combination, with the addition of immunotherapy, based on the benefit of added immunotherapy in the first-line setting (provided that the patient maintains a good performance status ). Treatment regimens for newly diagnosed SCLC are discussed elsewhere. (See "Extensive-stage small cell lung cancer: Initial management", section on 'Initial treatment'.)

Single-agent chemotherapy is an alternative for those who are not candidates for or would prefer not to undergo combination chemotherapy. (See 'Lurbinectedin' above and 'Camptothecins, as an alternative' above.)

Data regarding reinduction using a combination platinum-based therapy are as follows:

Support for reinduction with the original platinum regimen comes from a retrospective analysis of 81 patients who received second-line chemotherapy for SCLC that was relapsed after 90 days (sensitive relapse) [15]. Of these, 67 were treated with rechallenging of platinum-based regimens; 14 were treated with other regimens. The median treatment-free interval prior to second-line treatment was 182 days in the rechallenge group and 197 days in the small non-rechallenge group. Median progression-free survival (PFS) was 5.1 months in the rechallenge group and 3.4 months in the group that was not rechallenged with platinum-based chemotherapy, and median survival was 10.7 and 8.2 months, respectively. However, these differences were not statistically significant.

In a multicenter retrospective review, 112 patients had sensitive relapse treated with platinum and etoposide rechallenge [16]. The response to rechallenge chemotherapy was complete response in 3 percent, partial response in 42 percent, and stable disease in 19 percent. The median PFS and overall survival (OS) were 5.5 and 7.9 months, respectively, from the time of rechallenge. Although there was no statistically significant difference in PFS or OS between patients with treatment-free intervals between 90 and 150 versus ≥150 days, the number of patients with treatment-free intervals less than 150 days was very small (n = 21).

Other data support the use of combination platinum-based chemotherapy over single-agent topotecan in those with relapse after 90 days [17,18]. For example, in a randomized trial in 164 patients with relapse at least 90 days after platinum-etoposide treatment, patients assigned to carboplatin and etoposide (CE) had a longer median PFS relative to those assigned to topotecan (4.7 versus 2.7 months, hazard ratio [HR] 0.57, 90% CI 0.41-0.73) [18]. In subset analysis, the patients who got carboplatin and etoposide >180 days after initial treatment had greater benefit with CE over topotecan (HR 0.23) than patients whose time to progression was between 90 and 180 days (HR 0.70). The most frequent grade 3 to 4 adverse events were neutropenia (14 percent in the combination chemotherapy group versus 22 percent in the topotecan group), thrombocytopenia (31 versus 36 percent), anemia (25 versus 21 percent), febrile neutropenia (6 versus 11 percent), and asthenia (9 versus 10 percent). Two treatment-related deaths occurred in the topotecan group (both were febrile neutropenia with sepsis), and no treatment-related deaths occurred in the combination group.

TREATMENT DURATION — While the optimal duration of second-line treatment has not been clearly established, a commonly employed and acceptable approach is to continue treatment until disease progression or unacceptable toxicity occurs.

THIRD-LINE TREATMENT

Tarlatamab — Tarlatamab, is a bispecific T-cell engager immunotherapy that directs the patient's T cells to cancer cells expressing delta-like ligand 3 (overexpressed in approximately 90 percent of SCLCs). It is approved by the US Food and Drug Administration (FDA) for patients with extensive stage SCLC with disease progression on or after platinum-based chemotherapy and at least one other line of therapy, at a dose of 10 mg intravenously every two weeks (after an initial "step-up" dosing schedule) [19]. The approval is based on response rates and is contingent upon results of a confirmatory trial.

Tarlatamab has shown promising activity in a phase II trial among patients with disease that had relapsed after, or was refractory to, one platinum-based treatment regimen and at least one other line of therapy. At a dose of 10 mg intravenously every two weeks, the response rate was 40 percent, median progression-free survival was 4.9 months, and overall survival was 14.3 months [20]. The most common adverse events in these patients were cytokine-release syndrome (CRS; in 51 percent), decreased appetite (29 percent), and pyrexia (35 percent). Grade 3 CRS occurred in 1 percent.

In a pooled safety analysis reported in the FDA label [19]:

CRS occurred in 55 percent, mostly occurring during treatment cycle 1. The median time to onset of any grade CRS from last exposure to tarlatamab was 13.5 hours. CRS can manifest as pyrexia, hypotension, fatigue, tachycardia, headache, hypoxia, nausea, and vomiting. Potentially life-threatening complications of CRS include cardiac dysfunction, acute respiratory distress syndrome, neurologic toxicity, kidney and/or hepatic failure, and disseminated intravascular coagulation. Management of CRS is discussed elsewhere. (See "Cytokine release syndrome (CRS)" and "Cytokine release syndrome (CRS)", section on 'Management'.)

Neurologic toxicity occurred in 47 percent, including 10 percent with grade 3 toxicity. The most frequent neurologic toxicities included headache (14 percent), peripheral neuropathy (7 percent), dizziness (7 percent), and insomnia (6 percent). Immune effector cell-associated neurotoxicity syndrome (ICANS), which can present as confusion, lethargy, or disorientation (among other symptoms) occurred in 9 percent. It most frequently occurred following cycle 2 day 1 and had a median time of onset from first dose of 29.5 days. Further discussion of clinical features and management of ICANS is found elsewhere. (See "Immune effector cell-associated neurotoxicity syndrome (ICANS)".)

LATER-LINE OPTIONS — Treatment may be offered to patients who still have adequate performance status after progression on three lines of therapy (Eastern Cooperative Oncology Group [ECOG] performance status [PS] 0 to 2), at the discretion of the treating clinician and depending on patient preferences (table 1). Subsequent treatment is generally less effective, but it can provide significant palliation for many patients. Symptom control and improved quality of life are the primary goals of treatment, and these must be clear to both patients and their families. While treatment has been associated with improved quality of life outcomes, other benefits include possibly prolonged survival, increased time to tumor progression, and a reduction in tumor [5,21,22]. For those with a poor performance status (ECOG PS 3 or 4 (table 1)), we offer palliative symptom management. (See 'Poor performance status' below.)

Treatment options will depend on what the patient previously received. For example, if the patient has not yet received a camptothecin, this would be the preferred option (see 'Camptothecins, as an alternative' above). A number of other agents, including the taxanes, vinorelbine, gemcitabine, and temozolomide, have shown activity in patients with relapsed SCLC, typically with response rates among previously treated patients on the order of 20 to 30 percent for the taxanes and 10 to 15 percent for the other agents. Additionally, amrubicin has shown comparable activity to topotecan but is only available in Japan and has a high frequency of hematologic toxicity. The evidence for activity of these agents comes from small, single-arm phase II trials conducted 10 or more years ago. For patients who have progressed on or are intolerant of lurbinectedin and a camptothecin, a choice of agents depends on the side-effect profile of the agent and patient and provider preferences.

Paclitaxel — Paclitaxel is a later-line option after camptothecins given the response rates associated with this agent, though there are no data comparing paclitaxel with other agents in this setting. Treatment considerations include the risk of neuropathy associated with paclitaxel as well as steroid premedication and its associated risks. Paclitaxel has demonstrated response rates of approximately 30 percent in small, prospective studies. In a study of 24 patients with refractory disease, paclitaxel (175 mg/m2 every 21 days) resulted in seven partial responses (29 percent). However, the duration of response was generally brief (median, 100 days), and there were four toxic deaths [23]. Another study evaluated 21 patients using paclitaxel 80 mg/m2 weekly for six of eight weeks [24]. Objective responses were seen in 3 of 11 patients with sensitive relapse and 2 of 10 patients with refractory relapse.

Other options — Next options include gemcitabine, temozolomide, and vinorelbine. Given comparable efficacy among these agents, a choice among them must take into account the relative side effect profiles. Gemcitabine causes myalgias and flu-like symptoms, while vinorelbine is more frequently associated with neuropathy and requires a central line because of the risk of extravasation. Both can cause myelosuppression, with gemcitabine being associated with higher rates of thrombocytopenia. Temozolomide is associated with gastrointestinal side effects, including nausea, vomiting, loss of appetite, and constipation. The disease outcomes associated with these agents are outlined below:

GemcitabineGemcitabine (1000 mg/m2 on days 1, 8, and 15 of each 28-day cycle) has demonstrated response rates of 12 percent among patients with either refractory/resistant or sensitive relapsed disease, with an overall median survival of 7.1 months [25]. In a separate study evaluating a higher dose (1250 mg/m2), the response rates were 16 percent among 15 patients with sensitive relapse and 6 percent among 12 patients with refractory relapse, with median survivals of 8.8 and 4.2 months, respectively [26].

Temozolomide – In a phase II study of 64 patients (48 with sensitive disease and 16 with refractory disease), 1 complete response and 10 partial responses were observed, for an overall objective response rate of 16 percent [27].

Vinorelbine – Response rates with vinorelbine (30 mg/m2 weekly) have been on the order of 16 percent among those with sensitive relapse and 12.5 percent in those with relapsed or refractory disease [25,28].

Amrubicin is not approved for use in the United States but may be an acceptable option in Japan, where it is available. Rates of grade 3 to 4 neutropenia are high, however, with this agent. In a phase III trial, 637 patients with sensitive, resistant, or refractory relapse were randomly assigned in a 2:1 fashion to amrubicin (40 mg/m2 days 1 to 3 every three weeks) or topotecan (1.5 mg/m2 intravenously days 1 to 5 every three weeks) [29]. There was no difference in overall survival (OS; 7.5 months for amrubicin and 7.8 months for topotecan). Response rate and progression-free survival (PFS) significantly favored amrubicin. Symptom control and quality of life were also better for patients receiving amrubicin. In patients with resistant or refractory SCLC, a significant improvement in OS was seen for amrubicin (median, 6.2 versus 5.7 months with topotecan; hazard ratio 0.77). In terms of toxicity, amrubicin was associated with a higher infection and febrile neutropenia rate than topotecan but had less anemia, neutropenia, and thrombocytopenia.

Although nivolumab and pembrolizumab had previously been considered as single-agent options for later-line therapy in metastatic SCLC [30-33] (and are still supported by the National Comprehensive Cancer Network for select patients who have not previously received immune checkpoint inhibitors [34]), they are no longer approved by the US Food and Drug Administration in this setting [21,35], given failure to demonstrate improvement in survival relative to chemotherapy [36].

SPECIAL CONSIDERATIONS

Poor performance status — For patients with a poor performance status (Eastern Cooperative Oncology Group performance status [PS] 3 or 4 (table 1)) with progression on initial therapy, symptom management including palliative radiation is offered. There are no data to inform the use of further lines of systemic therapy in this population. (See "Stereotactic body radiation therapy for lung tumors".)

Patients with brain metastases — Both the primary tumor and systemic metastases in patients with SCLC are generally chemosensitive, at least initially. A number of individual agents and combinations are highly active in this disease. (See "Extensive-stage small cell lung cancer: Initial management".)

The reported responses of brain metastases to systemic chemotherapy in previously untreated patients are discussed elsewhere. (See "Extensive-stage small cell lung cancer: Initial management", section on 'Patients who present with brain metastases'.)

Response rates in previously treated patients with brain metastases range between 22 and 50 percent and are comparable to the response rates with second-line chemotherapy observed in extracranial disease [37-42]. As many patients with SCLC have received prior whole-brain radiation therapy (WBRT), either therapeutically or in the form of prophylactic cranial irradiation, further radiation options at the time of brain relapse may be limited. Systemic therapies that may be considered in the setting of recurrent brain metastases from SCLC based on case series and phase II studies include:

Topotecan [40]

Carboplatin and/or irinotecan [41,43,44]

Temozolomide [27]

Of note, lurbinectedin has not been evaluated in patients with brain metastases.

Adding WBRT to chemotherapy may increase the response rate of the brain metastases, but does not appear to improve survival and has not been widely adopted. In a phase III trial conducted by the European Organisation for Research and Treatment of Cancer, 120 patients with SCLC and brain metastases were randomly assigned to treatment with the chemotherapy agent teniposide alone or with WBRT [45]. Patients treated with the combination of chemotherapy and WBRT had a significantly higher response rate (57 versus 22 percent with chemotherapy alone), but overall survival was not improved (3.5 versus 3.2 months). Most of the patients in this trial had received prior chemotherapy (73 percent). Of note, teniposide has limited commercial availability. Temozolomide has also been studied in combination with WBRT in various histologies but is not routinely used in this setting.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Diagnosis and management of lung cancer".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Small cell lung cancer (The Basics)")

Beyond the Basics topics (see "Patient education: Small cell lung cancer treatment (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Introduction – Although considered highly responsive to chemotherapy and radiotherapy, small cell lung cancer (SCLC) usually recurs within 14 to 15 months for patients with limited-stage SCLC and 5 to 6 months for patients with extensive-stage SCLC. Many of these patients are candidates for additional systemic treatment. (See 'Introduction' above.)

Patients with relapse within six months of treatment – For patients with extensive SCLC who experience progression on or within six months of initial chemotherapy, we suggest treatment with lurbinectedin (Grade 2C), but camptothecins are an acceptable alternative. Lurbinectedin has a milder toxicity profile than the camptothecins, but may not be widely available. (See 'Lurbinectedin' above and 'Camptothecins, as an alternative' above.)

Patients with relapse more than six months from treatment – For those in whom relapse occurred more than six months from front-line treatment with standard platinum-based doublet chemotherapy, we suggest reinduction with the original or a novel platinum-based combination (Grade 2C), provided that the patient maintains a good performance status (Eastern Cooperative Oncology Group [ECOG] performance status [PS] 0 to 2 (table 1)).

For those on maintenance immunotherapy, some, but not all, UpToDate experts continue immunotherapy with chemotherapy.

For patients who are immunotherapy naïve, we also suggest addition of an immune checkpoint inhibitor (Grade 2C), extrapolating from the front-line setting. (See 'Patients with relapses >6 months after treatment (late relapse)' above.)

For patients with a poor performance status (ECOG PS 3 or 4 (table 1)) with progression on or after initial therapy, symptom management including palliative radiation is offered (eg, standard external-beam radiation to bone, mediastinum, brain, etc). There are no data to inform the use of further lines of systemic therapy in this population. (See "Stereotactic body radiation therapy for lung tumors".)

Third-line treatment – Upon second progression, tarlatamab should be considered for eligible patients. (See 'Tarlatamab' above.)

Later line options – Upon subsequent progression, additional lines of therapy are generally less effective than the initial treatment, but can provide significant palliation for many patients. Symptom control and improved quality of life are the primary goals of treatment. For patients who remain candidates for further treatment, we offer single-agent chemotherapy rather than combination chemotherapy or immunotherapy. (See 'Paclitaxel' above and 'Other options' above.)

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Topic 4614 Version 51.0

References

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