YSQTG Combined With Immuno-chemotherapy for Extensive-Stage Small Cell Lung Cancer

Yishen Qutong Granules Combined With Immunochemotherapy for Extensive-Stage Small Cell Lung Cancer: A Multicentre, Randomised, Triple-Blind, Placebo-Controlled Trial

Globally, lung cancer stands as the foremost cause of cancer-related mortality. Among its subtypes, small cell lung cancer (SCLC) represents an exceptionally aggressive malignancy, accounting for approximately 15-20% of all lung cancer cases. Over two-thirds of SCLC patients are diagnosed at an extensive stage, facing a median survival of only 7-12 months, a 2-year survival rate below 5%, and a dismal 5-year survival rate of 2%, underscoring its poor prognosis and high mortality. First-line treatment for extensive-stage SCLC typically involves comprehensive therapy centered on chemotherapy, often combined with immunotherapy. While this approach can achieve response rates of 50-70%, it is frequently accompanied by significant adverse effects, including bone marrow suppression and debilitating gastrointestinal reactions such as nausea, vomiting, and anorexia. The considerable toxicity associated with chemotherapy poses a major clinical challenge, limiting the potential for dose or duration escalation and hindering further efficacy gains. Therefore, developing strategies to mitigate toxicity while enhancing therapeutic efficacy remains an urgent clinical priority.

In the paradigm of Traditional Chinese Medicine (TCM), extensive-stage SCLC is categorized under syndromes such as "pulmonary accumulation," "cough," and "consumptive disease." Its fundamental pathogenesis is characterized by a deficiency of healthy qi (vital energy) alongside an excess of pathogenic factors, primarily "toxins," "stasis," and "phlegm." The core pathological mechanism involves the internal accumulation of toxins, disruption of the lung's dispersing and descending functions, disharmony of qi and blood, and consequent depletion of vital qi over time. Treatment strategies thus aim to resolve toxins, dispel stasis, and reinforce the body's vital qi. Preliminary clinical observations suggest that the TCM formula Yishen Qutong Granules, developed based on the theories of "reinforcing healthy qi to resolve toxins" and the "metal-water mutual generation" principle, can significantly alleviate symptoms in SCLC patients. Building on this foundation, the present study proposes to evaluate the integration of Yishen Qutong Granules with standard chemo-immunotherapy for extensive-stage SCLC, with the objectives of improving patients' quality of life and extending overall survival.

To this end, investigators will conduct a multicenter, randomized, triple-blind, placebo-controlled clinical trial. A total of 308 patients with extensive-stage SCLC, who are scheduled to undergo first-line immunotherapy combined with etoposide and platinum-based chemotherapy, will be enrolled from participating centers. Participants will be randomly allocated in a 1:1 ratio to either the treatment group or the control group (n=154 each). The treatment group will receive oral Yishen Qutong Granules (10g, three times daily) in addition to the standard chemo-immunotherapy regimen. The control group will receive an identical regimen of standard therapy along with a matched placebo granule. The intervention period for the herbal preparation/placebo is 90 days, and all patients will be followed for 18 months. The primary efficacy endpoint is the Disease Control Rate (DCR). Secondary endpoints include Overall Survival (OS), Progression-Free Survival (PFS), TCM syndrome score (assessed using a validated scale), St. George's Respiratory Questionnaire (SGRQ) score, EORTC QLQ-C30 quality of life score, cancer-related fatigue, and emotional status. Safety will be rigorously monitored through serial assessments of routine blood/urine/stool tests, hepatic and renal function panels, and electrocardiograms. This study aims to generate high-level evidence for the integrative TCM-Western medicine approach and elucidate the potential role of Yishen Qutong Granules in the comprehensive management of extensive-stage SCLC.

Inclusion Criteria:

• Meets Western medical diagnostic criteria for extensive-stage small cell lung cancer and Chinese medicine diagnostic criteria for kidney deficiency with qi deficiency and stagnation of blood stasis;
• Newly diagnosed extensive-stage small cell lung cancer patients who have not previously received Western medical antineoplastic therapy, with evaluable lesions;
• Intended to receive ≥2 cycles of first-line immunotherapy plus platinum-based chemotherapy plus etoposide;
• No concurrent or prior history of other primary malignancies;
• Aged ≥18 years with an estimated survival period of ≥3 months;
• Karnofsky Performance Status (KPS) ≥60 points;
• Normal cognitive function sufficient to complete questionnaires;
• Voluntary acceptance of the study treatment regimen and signing of informed consent.

Exclusion Criteria:

• Pregnant or breastfeeding women, or individuals with severe diseases affecting the cardiovascular, pulmonary, hepatic, renal, or haematological systems;
• Participants in other clinical trials.