The most common side effect during CCRT is blood cell toxicity. In severe cases, it can induce FN, and the immune decline triggers infections and can even be life-threatening [18, 19]. At present, rhG-CSF and PEG-rhG-CSF are routinely used in antitumor adjuvant therapy, and PEG-rhG-CSF has shown more strengths. A large number of domestic and international studies have confirmed that PEG-rhG-CSF has similar efficacy to rhG-CSF but has superior safety in the prophylactic treatment of chemotherapy-induced non-myeloid-derived neutropenia [20–24]. RhG-CSF requires daily administration because of its short half-life [25–27]. However, PEG-rhG-CSF is a long-acting, self-regulating rhG-CSF that has reduced plasma clearance and prolonged half-life compared to rhG-CSF, with only one dose required per chemotherapy cycle [26, 28, 29]. Therefore, it is more favorable for clinical treatment.
Research has shown that concurrent use of chemotherapy and administration of hematological growth factors may enhance hematological toxicity . The initial evidence came from a multicenter prospective trial by the Southwest Oncology Group . The results show that patients administered GM-CSF had higher WBC counts and ANCs, but there was no significant difference in the incidence of grade IV leukopenia or neutropenia. However, there was a statistically significant increase in the incidences of thrombocytopenia and anemia in the GM-CSF arm. The rates of infection and toxicity-related death were also higher in GM-CSF patients.
Early studies focused on GM-CSF, which does not act specifically on granulocyte progenitors, and it is no longer a routine treatment used to raise leukocyte counts. Therefore, it is necessary to re-evaluate the safety of granulocyte-stimulating factors. Some studies have shown that the use of granulocyte-stimulating factors is justified . In addition, a randomized controlled trial and meta-analysis indicated that the incidences of neutrophil deficiency and FN were significantly improved with the use of long-acting G-CSF . Goodman Lindsey Martin et al analyzed the prophylactic use of PEG-rhG-CSF in 180 patients with NSCLC receiving new chemotherapy regimens and showed a significant reduction in the FN risk . In the past, G-CSF was given to patients deemed to be at high risk of developing hematological toxicity. However, the results of the available studies contradict previous perceptions. Patients treated with G-CSF have significantly lower hematological toxicity and may have better treatment efficacy. The results of our trial further confirm this.
A phase II clinical trial of prophylactic application of G-CSF in 38 patients with limited-stage SCLC treated with CCRT did not show an increased risk of acute or advanced pulmonary toxicity or grade III-IV acute esophagitis, nor did it result in treatment-related mortality in patients. There was no significant difference in the incidence of neutropenia, but the incidence of grade III/IV adverse events was slightly lower than that in the non-preventive use group. However, prophylactic application of G-CSF increased the risk of thrombocytopenia . This result is similar to that of the trial by the Southwest Oncology Group. Our study suggests that the PLT counts is decreased with PEG-rhG-CSF administration, and the decrease after therapy was still lower than that in patients not treated with PEG-rhG-CSF. The grade III-IV thrombocytopenia incidence was lower than in patients who did not use PEG-rhG-CSF. Although there was no difference in the PLT count, there were also no bleeding events due to thrombocytopenia during the treatment. Therefore, the reduction in the PLT count may be a manifestation of myelosuppression and not closely related to PEG-rhG-CSF administration. CONVERT is a phase III randomized controlled trial involving 547 patients with SCLC treated with CCRT . Of the patients, 33% received at least one cycle of prophylactic G-CSF, and 41% received therapeutic G-CSF. The application of G-CSF during CCRT did not increase the risk of acute esophagitis or pulmonary toxicity and facilitated treatment completion. In contrast, there was a predominance of grade I and II esophagitis, with very few patients having symptoms of pneumonia and no cases of severe pulmonary toxicity or esophagitis in our study. The patients received appropriate therapy to alleviate these reactions during treatment and did not feel otherwise unwell. Therefore, these research findings indicate that the administration of PEG-rhG-CSF is reliable in terms of safety and efficacy. It is feasible to prophylactically administer granulocyte-stimulating factor.
Previous studies by the Southwest Oncology Group have shown that the median survival duration is slightly shorter in G-CSF-treated patients than in patients treated without G-CSF. However, G.H. Lyman et al conducted a systematic review and meta-analysis of the effect of G-CSF on the chemotherapy dose and survival of oncology patients . Patients treated with G-CSF had reduced all-cause mortality. Liu Fang performed a retrospective study of 33 patients with non-small-cell lung cancer (NSCLC) who had previously developed FN, and 29 patients received PEG-rhG-CSF prophylactically at the start of the next cycle of chemotherapy . The median PFS and OS times for patients treated with and without PEG-rhG-CSF prophylactically were 177 and 163 days (PFS; P=0.20), 628 days and 274 days (OS; P=0.13), respectively, which are similar to the results of our study. These results further illustrate the reliability of PEG-rhG-CSF. Prophylactic use of PEG-rhG-CSF may reduce the probability of radiotherapy-related adverse events and make oncology treatment safe and effective. More importantly, it had no significant impact on survival time.
Our study focused on hematological toxicity with PEG-rhG-CSF administration during CCRT. The results showed that prophylactic application of PEG-rhG-CSF significantly reduced the incidences of leukopenia and neutropenia, especially the incidences of grade III-IV leukopenia and neutropenia. More importantly, there were no significant differences in the incidences of grade III-IV thrombocytopenia and anemia between the groups, and there were no cases of blood transfusion, death or other serious adverse events. Furthermore, on the 10th day after chemotherapy, the experimental group achieved the peak ANC and thereafter maintained normal neutrophil levels, while the control group showed varying degrees of reduction despite regular administration of rhG-CSF. Importantly, the number of patients with radiotherapy interruptions was significantly lower in the experimental group than in the control group. In addition, the incidence of FN was also significantly decreased, and the incidences of all other adverse reactions were within the control ranges. There was also no significant acute esophagitis or pulmonary toxicity. Furthermore, no toxicity-related deaths were observed, and the results showed no effects on PFS or OS. These findings show that PEG-rhG-CSF has good reliability and compliance.