Chemotherapy For Recurrent Cervical Cancer Research Articles

Patterns of pembrolizumab use for recurrent cervical cancer.

e17528 Background: Pembrolizumab was approved for treatment of recurrent or metastatic cervical cancer (CC) as a single agent after chemotherapy in 2018 and in combination with chemotherapy in 2021, but little is known about how it has been actually used in clinical care. We examined real-world use of pembrolizumab for recurrent CC. Methods: The Merative MarketScan Research Databases were used to identify newly diagnosed CC patients who underwent primary hysterectomy or radiation between 2017-2022. Utilization of systemic therapy was assessed at the time of primary/adjuvant therapy and at first recurrence. Primary/adjuvant chemotherapy was defined as the use of chemotherapy within 4 months of the first cancer claim. First-line (1L) systemic therapy for recurrence was defined as the introduction of a new agent after a gap of > 3 months for patients who received adjuvant/primary chemotherapy or after 4 months from primary hysterectomy or radiation. Treatment for recurrence was classified as platinum alone, platinum-based combination therapy and non-platinum therapy. The use of targeted therapy (bevacizumab) and immunotherapy (pembrolizumab, nivolumab) was noted. Patterns and duration of use of each agent are described. Results: A total of 2727 patients were identified, including 1259 (46.2%) who underwent primary hysterectomy and 1468 (53.8%) treated with primary radiotherapy. Chemotherapy for recurrent CC was initiated in 339 patients (12.4%). Treatment for recurrence was noted in 9.7% of those treated initially with hysterectomy and in 14.8% of those with primary radiotherapy. Among patients treated for recurrence, 24.8% received platinum alone, 52.5% received a platinum-based combination, and 22.7% received non-platinum regimens. A total of 41 patients (12.1%) received pembrolizumab after recurrence, including 7.1% who received pembrolizumab alone, 2.1% who received pembrolizumab in combination with platinum, and 2.9% who received pembrolizumab with non-platinum therapy. Pembrolizumab was used after recurrence in 15.7% of patients who received chemotherapy during primary therapy compared to 7.1% of those who did not receive primary chemotherapy. Use of pembrolizumab was 11.4% in 2018, 17.6% in 2019, 14.0% in 2020, 8.8% in 2021, and 11.8% in 2022. The median duration of 1L chemotherapy for recurrence was 2.3 months (IQR, 1.0-5.8) overall, and 4.3 months (IQR, 2.4, 9.8) for patients treated with pembrolizumab. Patients who had not received primary/adjuvant chemotherapy had a longer duration of treatment with pembrolizumab than those who had received upfront chemotherapy, median 7.5 (IQR 3.9-9.8) versus 4.0 (IQR 2.2-11.0) months, respectively. Conclusions: Platinum-based chemotherapy remains the predominant therapy for recurrent CC. Pembrolizumab use is increasing for patients with recurrent cervical cancer. Longer follow-up is necessary to further evaluate its post-approval usage.

Penetrating complications of bevacizumab-containing chemotherapy in previously-irradiated recurrent cervical cancer: a Korean multicenter retrospective study of the Gynecologic Oncology Research Investigators coLLaborAtion (GORILLA) group (GORILLA1001) (036)

<b>Objectives:</b> Gynecologic Oncology Group 240 study showed that incorporating bevacizumab in the treatment of recurrent, persistent, or metastatic cervical cancer conferred overall survival (OS) benefit. However, fistula occurred significantly higher in the bevacizumab (+) group than the chemotherapy alone group. Moreover, all fistulas in the bevacizumab (+) group were developed in patients who were previously irradiated. This study aimed to evaluate the incidence and to identify risk factors for penetrating complications, including gastrointestinal (GI) and genitourinary (GU) fistula/perforation, of bevacizumab plus chemotherapy in recurrent cervical cancer patients who underwent pelvic radiation therapy (RT). <b>Methods:</b> Medical records of the patients with recurrent cervical cancer who previously underwent pelvic radiation at five university hospitals in Korea from 2007 to 2020 were retrospectively reviewed. Women who received chemotherapy immediately after RT were excluded. Clinical-pathologic factors were compared between groups of the following two settings: <i>1)</i> fistula/perforation (+) and (-); <i>2)</i> bevacizumab plus chemotherapy and chemotherapy alone. Univariate and multivariate regression analyses were performed to identify risk factors for penetrating complications. OS was also compared between groups of the two comparisons. <b>Results:</b> Of 219 women with recurrent cervical cancer who previously underwent pelvic RT, 144 (65.8%) received bevacizumab-containing chemotherapy, and 75 (34.2%) received chemotherapy alone. Fistula/perforation of any grade occurred in 36 (16.4%): fistulas alone in 27 (11 GI, 8 GU, and 8 both) and perforations in nine patients. Women receiving bevacizumab experienced fistula/perforation more frequently than those who used chemotherapy alone (20.8% [30/144] vs 8.0% [6/75]; p=0.015) (Table 1). Multivariate regression analysis showed that bevacizumab administration was the only independent risk factor for the occurrence of fistula/perforation. Age, diabetes, hypertension, tumor histology (squamous vs non-squamous), cumulative dose of RT, primary treatment (operation vs. RT vs both), use of intensity-modulated RT, and the time interval between RT and bevacizumab failed to show association with fistula/perforation. During median follow-up of 33.7 months (1.2-185.6 months), significant OS difference was shown neither between bevacizumab (+) versus bevacizumab (-) (HR: 1.03; median 119.8 months [95% CI: 97.3-142.3months] vs 115.7 months [96.0-135.4 months]; p=0.928) nor between fistula/perforation (+) versus fistula/perforation (-) (HR: 1.78; median 84.2 months [59.3-109.0 months] vs 129.5 months [114.1-144.9 months]; p=0.065). <b>Conclusions:</b> The study results suggest that incorporating bevacizumab in the chemotherapy regimen to treat recurrent cervical cancer with a previous history of pelvic RT incurs a considerable risk of GI and/or GU penetrating complications, which might damage the survival outcome as well as the quality of life. The risk and benefit of incorporating bevacizumab in the treatment of previously irradiated recurrent cervical cancer patients are needed to be carefully weighed, considering that effective prevention of the penetrating complications is difficult because of the lack of knowledge regarding other risk factors.

History of whole pelvis plus para-aortic radiation is a risk factor associated with febrile neutropenia during chemotherapy for recurrent cervical cancer.

Radiation-based therapy is widely used for advanced cervical cancer. Prior radiation-based therapy is a potential risk factor for febrile neutropenia (FN). However, the effect of irradiation field size on the incidence of FN during recurrent cervical cancer treatment is unclear. This study aimed to investigate the relationship between prior irradiation field size and FN development during recurrent chemotherapy. This retrospective, observational study included cervical cancer patients who received recurrent chemotherapy between November 2006 and June 2020. The patients were classified into two groups based on the area of irradiation fields. The first group included patients with a history of whole pelvis (WP) irradiation (WP group). The second group had patients who underwent WP plus para-aortic lymph node (PAN) irradiation (WP + PAN group). The incidences of hematological toxicities and FN during the recurrent chemoradiotherapy were compared between the two groups. The FN incidence was significantly higher in the WP + PAN group than in the WP group (32.1% vs. 0%, P < 0.001). The incidence of Grade 4 neutropenia was not significantly different between the WP + PAN and WP groups. The nadir absolute neutrophil counts were significantly lower and the dose reduction or discontinuation rate of chemotherapy was significantly higher in the WP + PAN group than in the WP group. History of WP plus PAN radiation is a risk factor for developing FN during recurrent cervical cancer chemotherapy.

First-line Chemotherapy for Recurrent Cervical Cancer

First-line Chemotherapy for Recurrent Cervical Cancer

Salvage radiotherapy with or without concurrent chemotherapy for pelvic recurrence after hysterectomy alone for early-stage uterine cervical cancer.

Treatment outcomes of patients with pelvic recurrence after hysterectomy alone for uterine cervical cancer who received salvage radiotherapy (RT) with or without concurrent chemotherapy were investigated. Salvage RT for recurrent cervical cancer confined to the pelvic cavity after hysterectomy alone was received by 33patients. The median interval between initial hysterectomy and recurrence was 26months. Whole-pelvic irradiation was delivered to median dose of 45 Gy, followed by aboost with amedian dose of 16 Gy to the gross tumor volume. Cisplatin-based concurrent chemotherapy was administered to 29patients. The median follow-up period was 53months for surviving patients. Most patients (97.0%) completed salvage RT of ≥45 Gy. Complete response (CR) was achieved in 23patients (69.7%). Pelvic sidewall involvement and evaluation with positron-emission tomography-computed tomography were significantly associated with CR. The 5‑year progression-free survival (PFS), local control (LC), distant metastasis-free survival (DMFS), and overall survival (OS) rates were 62.7, 79.5, 72.5, and 60.1%, respectively. Initial International Federation of Gynecology and Obstetrics stage, pelvic sidewall involvement, and CR status were significant factors for PFS and OS rates in multivariate analysis. The incidence of severe acute and late toxicities (≥grade3) was 12.1 and 3.0%, respectively. Aggressive salvage RT with or without concurrent chemotherapy for recurrent cervical cancer confined to the pelvic cavity was feasible, with promising treatment outcomes and acceptable toxicities. However, even more intensive novel treatment strategies should be investigated for patients with unfavorable prognostic factors.

Platinum-free Interval in Second-line Chemotherapy for Recurrent Cervical Cancer

The purpose of this study was to determine whether the platinum-free interval (PFI) was a predictive indicator in second-line treatment of cervical cancer in patients who had undergone prior platinum-based chemotherapy. The role of the PFI in selecting the second-line regimen in other gynecologic malignancies is also discussed. In this retrospective study, we examined the clinical records of patients with recurrent or metastatic cervical cancer who had received platinum-containing combination regimens as second-line chemotherapy. All patients had received prior platinum-containing chemotherapy or concurrent chemoradiotherapy. The overall response rate to second-line chemotherapy was 25.8%; 7 patients achieved a complete response and 17 a partial response. The median progression-free survival (PFS) was 5.1 months and median overall survival (OS) was 13.5 months. The response rate was 12.5%, 14.2%, 20.0%, 22.2%, and 55.0%; median PFS was 4.0, 5.1, 4.4, 5.8, and 7.4 months; and median OS was 10.2, 14.4, 11.9, 16.3, and 19.7 months when PFI was within 3, 3 to 5, 6 to 11, 12 to 23, and more than 24 months, respectively. Age (>50 years), size (>3 cm), prior radiotherapy, and PFI (>24 months) were identified as prognostic factors in the multivariate analysis for PFS and OS. The results indicate that a PFI of more than 24 months is the discriminating point between platinum-sensitive and platinum-resistance cervical cancer. This indicates that PFI offers a useful tool in selecting agents for second-line chemotherapy in a wide range of gynecologic malignancies.

Is a home-based palliative care treatment strategy preferable to standard chemotherapy in recurrent cervical cancer?

Is a home-based palliative care treatment strategy preferable to standard chemotherapy in recurrent cervical cancer?

Is a home-based palliative care treatment strategy preferable to standard chemotherapy in recurrent cervical cancer?

Objective: Recurrent cervical cancer (RCC) has a poor prognosis. Despite questionable benefit, treatment is often given at the expense of substantial toxicity. A panel of poor prognostic factors recently identified a high-risk group with an even worse prognosis. A prominent lung cancer study showed improved survival and quality of life (QOL) with treatment incorporation of home-based palliative care. We evaluated the comparative effectiveness of 4 management strategies for RCC: 1) standard combination chemotherapy for all (STD); 2) selective standard chemotherapy for low- to-intermediate risk patients, while high-risk patients receive home-based palliative care (SC); 3) single-agent chemotherapy plus home-based palliative care for all (C); and 4) home-based palliative care for all (H).

Are supportive care-based treatment strategies preferable to standard chemotherapy in recurrent cervical cancer?

ObjectiveRecurrent cervical cancer has a poor prognosis despite aggressive treatment. We evaluate the comparative-effectiveness of four management strategies in recurrent cervix cancer incorporating risk prognostication categories derived from pooled collaborative group trials: 1) standard doublet chemotherapy; 2) selective chemotherapy (home hospice with no chemotherapy for poorest prognosis patients with remainder receiving standard doublet chemotherapy); 3) single-agent chemotherapy with home hospice; and 4) home hospice. MethodsA cost-effectiveness decision model was constructed. Survival reduction of 24% was assumed for single-agent chemotherapy and 40% for hospice only compared to standard doublet chemotherapy. Overall survival and strategy cost for each arm were modeled as follows: standard doublet chemotherapy 8.9months ($33K); selective chemotherapy 8.7months ($29K); single-agent chemotherapy with home hospice 6.7months ($16K); and home hospice alone 5.3months ($11K). Base case analysis assumed equal quality of life (QOL). Sensitivity analyses assessed model uncertainties. ResultsStandard doublet chemotherapy for all is not cost-effective compared to selective chemotherapy with an incremental cost-effectiveness ratio (ICER) of $276K per quality-adjusted life-year (QALY). Sensitivity analysis predicted that a 90% improvement in survival is required before standard doublet chemotherapy is cost-effective in the poorest prognosis patients. Selective chemotherapy is the most cost-effective strategy compared to single-agent chemotherapy with home hospice with an ICER of $78K/QALY. Chemotherapy containing regimens become cost-prohibitive with small decreases in QOL. ConclusionsSupportive care based treatment strategies are potentially more cost-effective than the current standard of doublet chemotherapy for all patients with recurrent cervical cancer and warrant prospective evaluation.

Third-line salvage chemotherapy for recurrent cervical cancer.

e15510 Background: Recurrent cervical cancer with extrapelvic disease is incurable. Patients with recurrent disease may undergo multiple salvage chemotherapy regimens to prolong life or alleviate symptoms. There is limited data regarding efficacy and toxicity of chemotherapy in heavily pretreated cervical cancer patients. We describe the response rate, toxicity, progression-free survival (PFS) and overall survival (OS) in patients receiving 3rd line chemotherapy for recurrent cervical cancer. Methods: A chart review of patients at a single institution who, between 1/1/1995 and 1/1/2010, were diagnosed with recurrent or persistent cervical cancer and who received at least three different salvage regimens was performed. Response rates were measured using RECIST criteria. Toxicities were graded using the CTCAEv4.0. PFS and OS were calculated using Kaplan Meier curves. Results: 17 of 758 patients in the cervical cancer database met inclusion criteria. The median age was 43 (range 29-84). Third-line salvage regimens included vinorelbine (7 patients), paclitaxel (6) and others (4). The median number of cycles was 4 (range 1-11). One patient had a complete response and one had a partial response for a response rate of 12%. Common toxicities were anemia (82%, including 24% grade 3/4) and infection (35%, including 18% grade 3/4). Median PFS was 3.2 months (1.4-7 months), and median OS was 7.4 months (1.7-34.7 months). Median follow up from time of third-line treatment was 7 months (range 2-34). 6 patients (35%) went on to receive fourth-line chemotherapy. 16 patients (94%) are dead of disease. Conclusions: Third-line chemotherapy for recurrent cervical cancer has minimal activity and is associated with significant toxicity. Patients who have failed two salvage regimens are unlikely to derive further benefit from currently available agents. Consideration should be given to enrolling these patients in clinical trials or offering best supportive care.

Oral amino acids and testosterone therapy to improve muscle mass and quality of life during chemotherapy in recurrent cervical cancer: A case study

Muscle wasting is by far the most important phenotypic feature of cancer cachexia, though little success has been achieved toward reversing or preventing this catabolic process. Anabolic interventions including testosterone and amino acid supplements may be beneficial in reducing and/or reversing muscle wasting in these patient populations.A 48‐year‐old recurrent cervical cancer patient was scheduled to receive three 21‐day cycles of cisplatin and topotecan chemotherapy. She consented to a 10 week blinded interventional pilot study were she received daily amino acid supplements and weekly injections of testosterone enanthate before and during the weeks of chemotherapy treatment. Blood, Dual Energy X‐ray Absorptiometry (DEXA) scans, and Functional Assessment of Cancer Therapy ‐ General (FACT‐G) questionnaire data were collected before and after the 10 week period.Total serum testosterone concentrations, total and trunk lean body mass, and body weight increased after 10 weeks. Total and trunk fat mass decreased. FACT‐G scores improved.Concomitant treatment of oral amino acids and testosterone may be a viable therapeutic option for fighting cachexia and improving quality of life during chemotherapeutic treatment of recurrent cervical cancer. A double‐blinded, placebo‐controlled interventional study is in progress (NCT00878995).Funding through NIH/NCI RO1 CA127971 and T32 CA117834.

Salvage Chemotherapy in Recurrent Cervical Cancer With Biweekly Pegylated Liposomal Doxorubicin (Lipo-Dox)

To investigate the objective response rate to and tolerance of biweekly Lipo-Dox (TTY Biopharm Co. Ltd., Taipei, Taiwan) at a dosage of 20 mg/m(2) in previously treated patients with recurrent cervical cancer. This study was performed as a Simons two-stage phase II clinical trial. Ten patients with recurrent cervical cancer were enrolled between April 2003 and December 2005 at the Mackay Memorial Hospital. Lipo-Dox (20 mg/m(2) intravenous) diluted in 250 mL of 5% dextrose solution was administered at 2-weekly intervals. The mean age of the patients was 51 +/- 11.1 years. The mean number of cycles of Lipo-Dox injection was 4.6 (range, 1-12 cycles). Nine patients (90%) had disease progression. Only one patient (10%) achieved a partial response, and this was also the only patient who experienced WHO grade 2 palmar-plantar erythrodysesthesia, which led to treatment delay for 2 months. The median survival time was 2 months (range, 2-6 months). The majority of patients experienced grade 1 or 2 anemia (30%), leukopenia (20%) or thrombocytopenia (20%), and others exhibited symptoms of nausea and vomiting (30%). Salvage chemotherapy with Lipo-Dox at a dose of 20 mg/m(2) administered at 2-weekly intervals produced limited responses in patients with recurrent cervical cancer. This trial will not proceed to the second stage. These results may discourage the management of recurrent cervical cancer with single-agent Lipo-Dox in future clinical trials.

Chemotherapy for recurrent cervical cancer

Objective To give an overview of chemotherapy schemes used in recurrent cervical cancer. Methods A pubmed search was performed using chemotherapy and recurrent cervical cancer including articles until April 2007. Results Most recent articles and articles of interest are discussed. Conclusion Single agent cisplatin (50 mg/m 2) remains the current standard for recurrent cervical cancer. Numerous chemotherapeutic agents have been tested but did not show convincing evidence of improved survival rates, except for the GOG 179 study which showed an improved survival for the combination of cisplatin and topotecan compared with single agent cisplatin. However, nearly 60% of patients in both groups received prior cisplatinum therapy as a radiosensitizer, which could be responsible for the development of platinum resistance, causing lower response and survival rates in the single platinum group. Hence, the apparent benefit in the doublet group is maybe just a reflection from the change in primary therapy and patient population. It is hoped that current trials comparing standard therapy with other single or doublet chemotherapeutic regimens or that the use of molecular-targeted agents will give us promising therapeutic options in the future.

Prospective phase I/II study of irradiation and concurrent chemotherapy for recurrent cervical cancer after radical hysterectomy

The purpose of the present study was to evaluate the long-term toxicity and efficacy of irradiation and concurrent chemotherapy for patients with a pelvic recurrence of cervical cancer after a hysterectomy. This prospective phase I / II study was designed to administer irradiation and three cycles of concurrent chemotherapy with cisplatin and 5-FU to patients with recurrent cervical cancer confined to the pelvis. Initial therapy was a hysterectomy and none received prior pelvic irradiation. A total of 22 patients were entered into the study. Patients received irradiation and three cycles of concurrent cisplatin and 5-FU. The acute toxicity from chemotherapy and irradiation was grade 3 in 18% and grade 4 in 9%. No patient died from a treatment-related complication. Follow-up times ranged from 7.2 to 17.6 years. At last follow-up, 14 patients died of metastatic cervical cancer and eight were alive. The 10- and 15-year overall survivals were 35%. Long-term complications included leg edema, vesico-vaginal, and recto-vaginal fistulae. Pelvic abscesses developed in three of the four patients with a fistula. By logistic regression, the only significant factor for survival was total irradiation dose (P= 0.04). In conclusion, long-term survival with this treatment regimen is possible but is accompanied by significant late toxicity.

Bleomycin, vincristine, and mitomycin C (BOM) as second-line treatment after failure of cis-platinum-based combination chemotherapy for recurrent cervical cancer

Bleomycin, vincristine, and mitomycin C (BOM) as second-line treatment after failure of cis-platinum-based combination chemotherapy for recurrent cervical cancer

Bleomycin, vincristine, and mitomycin C (BOM) as second-line treatment after failure of cis-platinum-based combination chemotherapy for recurrent cervical cancer

Seventeen patients with recurrent cervical cancer were prospectively treated with a combination of bleomycin, vincristine, and mitomycin C (BOM). All patients had previously failed a cis-platinum-containing combination regimen. There were no complete responses. Four patients had partial responses, six patients had stable disease, and seven patients had no response. The median length of survival for responders was the same as that for nonresponders (5 months). More than 50% of patients experienced significant toxicity. The combination of bleomycin, vincristine, and mitomycin C appears to be ineffective as a secondUne chemotherapy regimen against recurrent cervical cancer previously treated with cis-platinum.

Factors affecting the response of recurrent squamous cell carcinoma of the cervix to cisplatin.

From June 1977 to June 1987 74 patients were treated with cisplatin for recurrent squamous cell carcinoma of the cervix as the primary chemotherapeutic agent. Sixty-eight patients were evaluable for response or survival. Patients with disease confined to the chest had a 53% complete response rate with an overall response rate of 73%. Patients with localized pelvic recurrences or persistence demonstrated no complete responses and a 21% overall response rate. Isolated chest metastases are more likely to respond to cisplatin than pelvic recurrences (P = 0.0007); however, location of recurrence did not significantly alter survival (mean 22.7 months versus 14.1 months; P = 0.24.). Concomitant disease in other locations reduced the likelihood of response in the chest (P less than 0.05) by virtue of lack of response in those other sites. Lesion size, clinical stage, patient age, and duration from primary treatment to recurrence were not of significance with regard to response or survival. When evaluating response to chemotherapy in recurrent cervical cancer, location of metastasis and effect on survival must be considered.