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Readministration of Cancer Drugs in a Patient with Chemorefractory Metastatic Colorectal Cancer

Readministration of Cancer Drugs in a Patient with Chemorefractory Metastatic Colorectal Cancer Hindawi Case Reports in Oncological Medicine Volume 2020, Article ID 2351810, 4 pages https://doi.org/10.1155/2020/2351810 Case Report Readministration of Cancer Drugs in a Patient with Chemorefractory Metastatic Colorectal Cancer Tetsuro Kawagoe , Go Ikeda, Yu Oshiro, Yuta Maruki, Keiko Kaneko, and Katsuhiko Iwakiri Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School, Japan Correspondence should be addressed to Tetsuro Kawagoe; tetsuro@nms.ac.jp Received 28 March 2020; Revised 3 June 2020; Accepted 11 June 2020; Published 23 June 2020 Academic Editor: Ossama W. Tawfik Copyright © 2020 Tetsuro Kawagoe et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. A 63-year-old woman was admitted to our institution for severe pain in her right lower abdomen caused by the perforation of cecal cancer. She underwent emergency surgery, from which she was diagnosed with cecal carcinoma with liver, lung, and lymph node metastases. As she was taking aspirin to prevent cerebral infarction, anti-vascular endothelial growth factor (receptor) antibody and regorafenib therapy were not used. Thus, we started a modified FOLFOX 6+cetuximab regimen. This first-line treatment initially achieved a partial response (PR), but she then developed progressive disease (PD) after 14 months. We changed the regimen to FOLFIRI, followed by trifluridine/tipiracil, but her progression-free survival periods were 2.7 months and 1 month, respectively. Although we cycled through the available array of standard cancer drugs, the patient showed a good performance status, and some benefit from treatment still seemed plausible. We readministered the 5-fluorouracil oral preparation S-1, which maintained stable disease (SD) for 7 months. After PD emerged, we readministered the anti-epidermal growth factor receptor (EGFR) antibody panitumumab for 7.5 months of SD. Finally, 39 months after her diagnosis, she died from rapidly progressing disease. However, her relatively long survival implies that readministering drugs similar to those used in previous regimens might benefit patients with metastatic colorectal cancer. 1. Introduction selected patients can maintain good performance status (PS) and receive further chemotherapies. For such patients, there are limited further chemotherapeutic options. Here, Chemotherapy is usually the first-choice treatment for meta- we report a woman with mCRC who benefitted from the static colorectal cancer (mCRC). Relatively new cytotoxic agents (such as irinotecan and oxaliplatin) and molecular tar- reintroduction of S-1, an oral prodrug of 5-FU, and anti- st nd rd EGFR antibodies after receiving standard 1 -, 2 -, and 3 - geted agents (such as antibodies against vascular endothelial growth factor (receptor) (VEGF (R)) and epidermal growth line chemotherapies. factor receptor (EGFR)) have extended the median overall survival of patients with mCRC to more than 20 months 2. Case Presentation [1–3]. Guidelines recommend chemotherapy regimens with standard cancer drugs, such as 5-fluorouracil (FU), irinote- A 63-year-old woman with a medical history of hypertension can, oxaliplatin, anti-VEGF (R) or anti-EGFR antibodies, and cerebral infarction was admitted to our hospital with regorafenib, and trifluridine/tipiracil [4–6]. More recently, severe abdominal pain in October 2012. immunotherapy has become available for a minority of Computed tomography (CT) scan of the abdomen and patients with microsatellite instability-high tumors [7]. pelvis showed inflammation spread, abscess formation, Although patients who have cycled through these standard lymphadenopathy around the cecum, and a huge mass with chemotherapies are usually only treated palliatively, some multiple nodules in the liver (Figures 1(a) and 1(b)). A chest 2 Case Reports in Oncological Medicine 3. Discussion Although this was a case of unresectable CRC, its treatment can be considered successful because the patient survived for 39 months after diagnosis while maintaining good PS despite being unable to receive anti-VEGF (R) antibody ther- (a) (b) (c) apy. Because she survived for 14.5 months after cycling through standard cancer regimens, retreatment apparently Figure 1: Pelvic CT showed inflammation spread and abscess facilitated her relatively long survival. formation around the cecum (a). Abdominal CT showed a huge Several reports on readministering anticancer drugs mass and multiple nodules in the liver (b). Chest CT showed nodules in the lungs (c). Arrows: lesions. [8–16] have suggested that after a washout period, earlier-line drugs that were initially effective but then became ineffective might become effective again [11–15]. CT also revealed multiple pulmonary nodules (Figure 1(c)). Santini et al. reported cetuximab rechallenge to be signifi- She was clinically diagnosed with intestinal perforation cantly effective after a cetuximab-free interval with cyto- owing to cecal cancer and underwent emergency surgery. toxic chemotherapy [13]. Their hypothesis is as follows. She was intraoperatively diagnosed with obstruction of the If the anti-EGFR antibody was initially effective, it would appendicular root owing to cecal cancer, perforation of the have reduced EGFR-sensitive clonal cells and insensitive vermiform appendix, intraperitoneal abscess, and lymphade- clones predominate at the PD stage. Subsequent cytotoxic nopathy around the cecum and received an ileocecal resec- chemotherapy would reduce the number of insensitive tion, D1 lymph node dissection, and a peritoneal wash. clones, and at the time of PD, sensitive clones would grow After surgery, she was finally diagnosed with moderately dif- and become dominant again. As a result, the anti-EGFR ferentiated wild-type KRAS adenocarcinoma of the cecum antibody would become active again. Their hypothesis (stage: T3N1M1b, per the Union for International Cancer appears to be supported by the result of the CRICKET Control criteria). A microsatellite instability (MSI) test was trial [14], in which rechallenge treatment with cetuximab not performed. RAS and BRAF status were also not investi- was demonstrated to be effective, especially in patients gated. We initiated therapy using cetuximab (500 mg/m ; without RAS mutations in circulating tumor DNA. This 14-day cycle) and the mFOLFOX6 regimen (5-FU hypothesis implies that even if the readministered drug is 2 2 400 mg/m bolus injection; leucovorin (LV) 200 mg/m ,46h panitumumab rather than cetuximab, an effect can be continuous infusion with 5-FU 2400 mg/m ; and oxaliplatin expected because both drugs are anti-EGFR antibodies. 85 mg/m ; 14-day cycle) in October 2012. This treatment Panitumumab might also have been effective after cetuxi- resulted in 7.75 months of partial response (PR), followed mab because panitumumab is a fully human monoclonal by a stable disease (SD) period of 6.25 months and progressive antibody (MoAb), whereas cetuximab is a chimeric MoAb disease (PD) for a total progression-free survival (PFS) period consisting of ~30% mouse protein and may have a differ- nd of 14 months. As a 2 -line treatment, we started the FOLFIRI ent sensitivity to cancer. Few reports have investigated the 2 2 effect of panitumumab after progression on cetuximab in regimen (5-FU 400 mg/m bolus injection, LV 200 mg/m , 46 h continuous infusion with 5-FU 2400 mg/m , and irino- colorectal cancer patients. Marino et al. reported in their tecan 150 mg/m ; 14-day cycle), but she developed PD after retrospective study that treatment with panitumumab after 2.7 months. We started trifluridine/tipiracil (35 mg/m progression on cetuximab was effective because its PR and administered twice daily on Days 1–5 and Days 8–12 of SD rates were 5% and 25% in 20 patients, respectively, rd a 28-day cycle) as a 3 and the median PFS and OS were 5 and 8 months, respec- -line treatment, but this led to PD after 1 month. As this patient had a history of cerebral tively [15]. In contrast, Wadlow et al. reported no infarction and used antiplatelet drugs, anti-VEGF (R) anti- responders to panitumumab treatment after progression on cetuximab and a SD rate of 45% with a median dura- body and regorafenib therapies were contraindicated. Hence, at this stage, no new standard cancer drugs could tion of only 1.7 months in their single-arm phase II trial of 20 patients [16]. Because both of these trials were con- be tried. However, the patient’s general condition was still good, and she requested further chemotherapy. Therefore, ducted in a small number of patients, and panitumumab we readministered the 5-FU oral preparation S-1 treatment after progression on cetuximab was actually effective in our study, it is necessary to identify the type (80 mg/m , Days 1–28, 42-day cycle), which provided a 7-month SD period (Figure 2). When PD was again con- of cases in which panitumumab treatment after progression on cetuximab is effective in the future. S-1 was developed to firmed, we administered panitumumab (6 mg/kg once every 2 weeks) as an anti-EGFR antibody rechallenge. improve the therapeutic effect of tegafur, an oral fluoropyri- The patient achieved SD on this regimen for 7.5 months midine, by maintaining high 5-FU concentrations in plasma and tumors with less gastrointestinal toxicity by 5-chloro-4- (Figure 3). Finally, 39 months after her diagnosis, the patient died because of rapid disease progression. While dihydroxypyridine (CDHP) and potassium oxonate. In this receiving readministered drugs, her PS was well main- case, the mechanism by which S-1 (as an oral fluoropyrimi- tained; she suffered no grade ≥ 3 adverse events (per the dine agent) was effective after the 5-FU infusion regimen National Cancer Institute Common Toxicity Criteria, ver- became ineffective is unclear. Reportedly, the use of the FOLFOX regimen with 5-FU infusion enhances sion 4.0; Table 1). Case Reports in Oncological Medicine 3 (a) (b) (c) (d) Figure 2: Abdominal and chest CT before the administration of S-1 (a, b). Stable disease after therapy (c, d). Arrows: lesions in the liver. (a) (b) (c) (d) Figure 3: Abdominal and chest CT before the administration of panitumumab (a, b). Stable disease after therapy (c, d). Pulmonary metastasis was slightly reduced after panitumumab treatment. Arrows: lesions in the liver. Table 1: Treatment toxicities and performance status. mFOLFOX6+Cetu FOLFIRI Trifluridine/tipiracil S-1 Panitumumab Grade 1/2 Decreased WBCs ○○ Decreased neutrophils ○○ Anemia ○○ ○ ○ ○ Decreased platelets ○○ Fever ○○ ○ ○ Anorexia ○○ ○ Dry skin ○ ○ Peripheral neuropathy ○○ Insomnia ○ Paronychia ○ ○ Fatigue ○○ ○ Mucositis oral ○○ Diarrhea ○ Rash acneiform ○ Grade 3 Decreased neutrophils ○ PS 1 1 2 1 1 Cetu: cetuximab; WBC: white blood cells. dihydropyrimidine dehydrogenase (DPD) activity in tumors Data Availability [17]. In the present case, S-1 may have maintained high levels of 5-FU in the tumor by suppressing DPD activity The clinical data used to support the findings of this study are enhanced by pretreatment with CDHP. included within the article. 4. Conclusion Conflicts of Interest In conclusion, we report a patient with metastatic CRC for whom repeated standard cancer treatments were effective We report no conflicts of interest. This research was per- despite prior development of refractory reactions. Why retreat- formed as part of the employment of the authors. The ment was effective remains unclear. Further research is needed. employer’s name is Nippon Medical School. 4 Case Reports in Oncological Medicine [13] D. Santini, B. Vincenzi, R. Addeo et al., “Cetuximab rechal- Acknowledgments lenge in metastatic colorectal cancer patients: how to come We thank Marla Brunker, from Edanz Group (https://en- away from acquired resistance?,” Annals of Oncology, vol. 23, author-services.edanzgroup.com/), for editing a draft of this no. 9, pp. 2313–2318, 2012. manuscript. [14] C. Cremolini, D. Rossini, E. Dell’Aquila et al., “Rechallenge for patients WithRASandBRAFWild-Type metastatic colorectal cancer with acquired resistance to first-line cetuximab and References Irinotecan,” JAMA Oncology, vol. 5, no. 3, pp. 343–350, 2019. [1] V. Heinemann, L. F. von Weikersthal, T. Decker et al., [15] A. Marino, C. Caliolo, F. Sponziello et al., “Panitumumab after “FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab progression on cetuximab inKRASWild-type metastatic colo- as first-line treatment for patients with metastatic colorectal rectal cancer patients: a single institution experience,” Tumori, cancer (FIRE-3): a randomised, open- label, phase 3 trial,” vol. 101, no. 5, pp. 524–528, 2015. The Lancet Oncology, vol. 15, no. 10, pp. 1065–1075, 2014. [16] R. C. Wadlow, A. F. Hezel, T. A. Abrams et al., “Panitumumab [2] F. Loupakis, C. Cremolini, G. Masi et al., “Initial therapy with in patients with KRASwild-type colorectal cancer after pro- FOLFOXIRI and bevacizumab for metastatic colorectal can- gression on cetuximab,” The Oncologist, vol. 17, no. 1, p. 14, cer,” The New England Journal of Medicine, vol. 371, no. 17, pp. 1609–1618, 2014. [17] H. Baba, M. Watanabe, H. Okabe et al., “Upregulation of [3] H. Baba, Y. Yamada, D. Takahari et al., “S-1 and oxaliplatin ERCC1 and DPD expressions after oxaliplatin-based first- (SOX) plus bevacizumab versus mFOLFOX6 plus bevacizu- line chemotherapy for metastatic colorectal cancer,” British mab as first-line treatment for patients with metastatic Journal of Cancer, vol. 107, no. 12, pp. 1950–1955, 2012. colorectal cancer: updated overall survival analyses of the open-label, non-inferiority, randomised phase III: SOFT study,” ESMO Open, vol. 2, no. 1, article e000135, 2017. [4] T. Watanabe, Japanese Society for Cancer of the Colon, K. M. Rectum et al., “Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorec- tal cancer,” International Journal of Clinical Oncology, vol. 23, no. 1, pp. 1–34, 2018. [5] A. B. Benson 3rd, A. P. Venook, L. Cederquist et al., “Colon cancer, version 1.2017, NCCN clinical practice guidelines in oncology,” Journal of the National Comprehensive Cancer Network, vol. 15, no. 3, pp. 370–398, 2017. [6] E. Van Cutsem, A. Cervantes, R. Adam et al., “ESMO consen- sus guidelines for the management of patients with metastatic colorectal cancer,” Annals of Oncology, vol. 27, no. 8, pp. 1386– 1422, 2016. [7] K. Jeught, H. C. Xu, Y. J. Li, X. B. Lu, and G. Ji, “Drug resis- tance and new therapies in colorectal cancer,” World Journal of Gastroenterology, vol. 24, no. 34, pp. 3834–3848, 2018. [8] G. Tonini, M. Imperatori, B. Vincenzi, A. M. Frezza, and D. Santini, “Rechallenge therapy and treatment holiday: differ- ent strategies in management of metastatic colorectal cancer,” Journal of Experimental & Clinical Cancer Research, vol. 32, no. 1, p. 92, 2013. [9] A. Hata, N. Katakami, S. Fujita et al., “Panitumumab rechal- lenge in chemorefractory patients with metastatic colorectal cancer,” Journal of Gastrointestinal Cancer, vol. 44, no. 4, pp. 456–459, 2013. [10] A. R. Townsend, S. Bishnoi, V. Broadbridge et al., “Rechallenge with oxaliplatin and fluoropyrimidine for metastatic colorectal carcinoma after prior therapy,” American Journal of Clinical Oncology, vol. 36, no. 1, pp. 49–52, 2013. [11] E. Ozaslan, A. O. Duran, O. Bozkurt et al., “Analyses of multi- ple factors for determination of "selected patients" who should receive rechallenge treatment in metastatic colorectal cancer: a retrospective study from Turkey,” Asian Pacific Journal of Cancer Prevention, vol. 16, no. 7, pp. 2833–2838, 2015. [12] C. Yeoh, I. Chau, D. Cunningham, A. R. Norman, M. Hill, and P. J. Ross, “Impact of 5-fluorouracil rechallenge on subsequent response and survival in advanced colorectal cancer: pooled analysis from three consecutive randomized controlled trials,” Clinical Colorectal Cancer, vol. 3, no. 2, pp. 102–107, 2003. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Case Reports in Oncological Medicine Hindawi Publishing Corporation

Readministration of Cancer Drugs in a Patient with Chemorefractory Metastatic Colorectal Cancer

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Copyright © 2020 Tetsuro Kawagoe et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Hindawi Case Reports in Oncological Medicine Volume 2020, Article ID 2351810, 4 pages https://doi.org/10.1155/2020/2351810 Case Report Readministration of Cancer Drugs in a Patient with Chemorefractory Metastatic Colorectal Cancer Tetsuro Kawagoe , Go Ikeda, Yu Oshiro, Yuta Maruki, Keiko Kaneko, and Katsuhiko Iwakiri Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School, Japan Correspondence should be addressed to Tetsuro Kawagoe; tetsuro@nms.ac.jp Received 28 March 2020; Revised 3 June 2020; Accepted 11 June 2020; Published 23 June 2020 Academic Editor: Ossama W. Tawfik Copyright © 2020 Tetsuro Kawagoe et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. A 63-year-old woman was admitted to our institution for severe pain in her right lower abdomen caused by the perforation of cecal cancer. She underwent emergency surgery, from which she was diagnosed with cecal carcinoma with liver, lung, and lymph node metastases. As she was taking aspirin to prevent cerebral infarction, anti-vascular endothelial growth factor (receptor) antibody and regorafenib therapy were not used. Thus, we started a modified FOLFOX 6+cetuximab regimen. This first-line treatment initially achieved a partial response (PR), but she then developed progressive disease (PD) after 14 months. We changed the regimen to FOLFIRI, followed by trifluridine/tipiracil, but her progression-free survival periods were 2.7 months and 1 month, respectively. Although we cycled through the available array of standard cancer drugs, the patient showed a good performance status, and some benefit from treatment still seemed plausible. We readministered the 5-fluorouracil oral preparation S-1, which maintained stable disease (SD) for 7 months. After PD emerged, we readministered the anti-epidermal growth factor receptor (EGFR) antibody panitumumab for 7.5 months of SD. Finally, 39 months after her diagnosis, she died from rapidly progressing disease. However, her relatively long survival implies that readministering drugs similar to those used in previous regimens might benefit patients with metastatic colorectal cancer. 1. Introduction selected patients can maintain good performance status (PS) and receive further chemotherapies. For such patients, there are limited further chemotherapeutic options. Here, Chemotherapy is usually the first-choice treatment for meta- we report a woman with mCRC who benefitted from the static colorectal cancer (mCRC). Relatively new cytotoxic agents (such as irinotecan and oxaliplatin) and molecular tar- reintroduction of S-1, an oral prodrug of 5-FU, and anti- st nd rd EGFR antibodies after receiving standard 1 -, 2 -, and 3 - geted agents (such as antibodies against vascular endothelial growth factor (receptor) (VEGF (R)) and epidermal growth line chemotherapies. factor receptor (EGFR)) have extended the median overall survival of patients with mCRC to more than 20 months 2. Case Presentation [1–3]. Guidelines recommend chemotherapy regimens with standard cancer drugs, such as 5-fluorouracil (FU), irinote- A 63-year-old woman with a medical history of hypertension can, oxaliplatin, anti-VEGF (R) or anti-EGFR antibodies, and cerebral infarction was admitted to our hospital with regorafenib, and trifluridine/tipiracil [4–6]. More recently, severe abdominal pain in October 2012. immunotherapy has become available for a minority of Computed tomography (CT) scan of the abdomen and patients with microsatellite instability-high tumors [7]. pelvis showed inflammation spread, abscess formation, Although patients who have cycled through these standard lymphadenopathy around the cecum, and a huge mass with chemotherapies are usually only treated palliatively, some multiple nodules in the liver (Figures 1(a) and 1(b)). A chest 2 Case Reports in Oncological Medicine 3. Discussion Although this was a case of unresectable CRC, its treatment can be considered successful because the patient survived for 39 months after diagnosis while maintaining good PS despite being unable to receive anti-VEGF (R) antibody ther- (a) (b) (c) apy. Because she survived for 14.5 months after cycling through standard cancer regimens, retreatment apparently Figure 1: Pelvic CT showed inflammation spread and abscess facilitated her relatively long survival. formation around the cecum (a). Abdominal CT showed a huge Several reports on readministering anticancer drugs mass and multiple nodules in the liver (b). Chest CT showed nodules in the lungs (c). Arrows: lesions. [8–16] have suggested that after a washout period, earlier-line drugs that were initially effective but then became ineffective might become effective again [11–15]. CT also revealed multiple pulmonary nodules (Figure 1(c)). Santini et al. reported cetuximab rechallenge to be signifi- She was clinically diagnosed with intestinal perforation cantly effective after a cetuximab-free interval with cyto- owing to cecal cancer and underwent emergency surgery. toxic chemotherapy [13]. Their hypothesis is as follows. She was intraoperatively diagnosed with obstruction of the If the anti-EGFR antibody was initially effective, it would appendicular root owing to cecal cancer, perforation of the have reduced EGFR-sensitive clonal cells and insensitive vermiform appendix, intraperitoneal abscess, and lymphade- clones predominate at the PD stage. Subsequent cytotoxic nopathy around the cecum and received an ileocecal resec- chemotherapy would reduce the number of insensitive tion, D1 lymph node dissection, and a peritoneal wash. clones, and at the time of PD, sensitive clones would grow After surgery, she was finally diagnosed with moderately dif- and become dominant again. As a result, the anti-EGFR ferentiated wild-type KRAS adenocarcinoma of the cecum antibody would become active again. Their hypothesis (stage: T3N1M1b, per the Union for International Cancer appears to be supported by the result of the CRICKET Control criteria). A microsatellite instability (MSI) test was trial [14], in which rechallenge treatment with cetuximab not performed. RAS and BRAF status were also not investi- was demonstrated to be effective, especially in patients gated. We initiated therapy using cetuximab (500 mg/m ; without RAS mutations in circulating tumor DNA. This 14-day cycle) and the mFOLFOX6 regimen (5-FU hypothesis implies that even if the readministered drug is 2 2 400 mg/m bolus injection; leucovorin (LV) 200 mg/m ,46h panitumumab rather than cetuximab, an effect can be continuous infusion with 5-FU 2400 mg/m ; and oxaliplatin expected because both drugs are anti-EGFR antibodies. 85 mg/m ; 14-day cycle) in October 2012. This treatment Panitumumab might also have been effective after cetuxi- resulted in 7.75 months of partial response (PR), followed mab because panitumumab is a fully human monoclonal by a stable disease (SD) period of 6.25 months and progressive antibody (MoAb), whereas cetuximab is a chimeric MoAb disease (PD) for a total progression-free survival (PFS) period consisting of ~30% mouse protein and may have a differ- nd of 14 months. As a 2 -line treatment, we started the FOLFIRI ent sensitivity to cancer. Few reports have investigated the 2 2 effect of panitumumab after progression on cetuximab in regimen (5-FU 400 mg/m bolus injection, LV 200 mg/m , 46 h continuous infusion with 5-FU 2400 mg/m , and irino- colorectal cancer patients. Marino et al. reported in their tecan 150 mg/m ; 14-day cycle), but she developed PD after retrospective study that treatment with panitumumab after 2.7 months. We started trifluridine/tipiracil (35 mg/m progression on cetuximab was effective because its PR and administered twice daily on Days 1–5 and Days 8–12 of SD rates were 5% and 25% in 20 patients, respectively, rd a 28-day cycle) as a 3 and the median PFS and OS were 5 and 8 months, respec- -line treatment, but this led to PD after 1 month. As this patient had a history of cerebral tively [15]. In contrast, Wadlow et al. reported no infarction and used antiplatelet drugs, anti-VEGF (R) anti- responders to panitumumab treatment after progression on cetuximab and a SD rate of 45% with a median dura- body and regorafenib therapies were contraindicated. Hence, at this stage, no new standard cancer drugs could tion of only 1.7 months in their single-arm phase II trial of 20 patients [16]. Because both of these trials were con- be tried. However, the patient’s general condition was still good, and she requested further chemotherapy. Therefore, ducted in a small number of patients, and panitumumab we readministered the 5-FU oral preparation S-1 treatment after progression on cetuximab was actually effective in our study, it is necessary to identify the type (80 mg/m , Days 1–28, 42-day cycle), which provided a 7-month SD period (Figure 2). When PD was again con- of cases in which panitumumab treatment after progression on cetuximab is effective in the future. S-1 was developed to firmed, we administered panitumumab (6 mg/kg once every 2 weeks) as an anti-EGFR antibody rechallenge. improve the therapeutic effect of tegafur, an oral fluoropyri- The patient achieved SD on this regimen for 7.5 months midine, by maintaining high 5-FU concentrations in plasma and tumors with less gastrointestinal toxicity by 5-chloro-4- (Figure 3). Finally, 39 months after her diagnosis, the patient died because of rapid disease progression. While dihydroxypyridine (CDHP) and potassium oxonate. In this receiving readministered drugs, her PS was well main- case, the mechanism by which S-1 (as an oral fluoropyrimi- tained; she suffered no grade ≥ 3 adverse events (per the dine agent) was effective after the 5-FU infusion regimen National Cancer Institute Common Toxicity Criteria, ver- became ineffective is unclear. Reportedly, the use of the FOLFOX regimen with 5-FU infusion enhances sion 4.0; Table 1). Case Reports in Oncological Medicine 3 (a) (b) (c) (d) Figure 2: Abdominal and chest CT before the administration of S-1 (a, b). Stable disease after therapy (c, d). Arrows: lesions in the liver. (a) (b) (c) (d) Figure 3: Abdominal and chest CT before the administration of panitumumab (a, b). Stable disease after therapy (c, d). Pulmonary metastasis was slightly reduced after panitumumab treatment. Arrows: lesions in the liver. Table 1: Treatment toxicities and performance status. mFOLFOX6+Cetu FOLFIRI Trifluridine/tipiracil S-1 Panitumumab Grade 1/2 Decreased WBCs ○○ Decreased neutrophils ○○ Anemia ○○ ○ ○ ○ Decreased platelets ○○ Fever ○○ ○ ○ Anorexia ○○ ○ Dry skin ○ ○ Peripheral neuropathy ○○ Insomnia ○ Paronychia ○ ○ Fatigue ○○ ○ Mucositis oral ○○ Diarrhea ○ Rash acneiform ○ Grade 3 Decreased neutrophils ○ PS 1 1 2 1 1 Cetu: cetuximab; WBC: white blood cells. dihydropyrimidine dehydrogenase (DPD) activity in tumors Data Availability [17]. In the present case, S-1 may have maintained high levels of 5-FU in the tumor by suppressing DPD activity The clinical data used to support the findings of this study are enhanced by pretreatment with CDHP. included within the article. 4. Conclusion Conflicts of Interest In conclusion, we report a patient with metastatic CRC for whom repeated standard cancer treatments were effective We report no conflicts of interest. This research was per- despite prior development of refractory reactions. Why retreat- formed as part of the employment of the authors. The ment was effective remains unclear. Further research is needed. employer’s name is Nippon Medical School. 4 Case Reports in Oncological Medicine [13] D. Santini, B. Vincenzi, R. Addeo et al., “Cetuximab rechal- Acknowledgments lenge in metastatic colorectal cancer patients: how to come We thank Marla Brunker, from Edanz Group (https://en- away from acquired resistance?,” Annals of Oncology, vol. 23, author-services.edanzgroup.com/), for editing a draft of this no. 9, pp. 2313–2318, 2012. manuscript. [14] C. Cremolini, D. Rossini, E. Dell’Aquila et al., “Rechallenge for patients WithRASandBRAFWild-Type metastatic colorectal cancer with acquired resistance to first-line cetuximab and References Irinotecan,” JAMA Oncology, vol. 5, no. 3, pp. 343–350, 2019. [1] V. Heinemann, L. F. von Weikersthal, T. Decker et al., [15] A. Marino, C. Caliolo, F. Sponziello et al., “Panitumumab after “FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab progression on cetuximab inKRASWild-type metastatic colo- as first-line treatment for patients with metastatic colorectal rectal cancer patients: a single institution experience,” Tumori, cancer (FIRE-3): a randomised, open- label, phase 3 trial,” vol. 101, no. 5, pp. 524–528, 2015. The Lancet Oncology, vol. 15, no. 10, pp. 1065–1075, 2014. [16] R. C. Wadlow, A. F. Hezel, T. A. Abrams et al., “Panitumumab [2] F. Loupakis, C. Cremolini, G. Masi et al., “Initial therapy with in patients with KRASwild-type colorectal cancer after pro- FOLFOXIRI and bevacizumab for metastatic colorectal can- gression on cetuximab,” The Oncologist, vol. 17, no. 1, p. 14, cer,” The New England Journal of Medicine, vol. 371, no. 17, pp. 1609–1618, 2014. [17] H. Baba, M. Watanabe, H. Okabe et al., “Upregulation of [3] H. Baba, Y. Yamada, D. Takahari et al., “S-1 and oxaliplatin ERCC1 and DPD expressions after oxaliplatin-based first- (SOX) plus bevacizumab versus mFOLFOX6 plus bevacizu- line chemotherapy for metastatic colorectal cancer,” British mab as first-line treatment for patients with metastatic Journal of Cancer, vol. 107, no. 12, pp. 1950–1955, 2012. colorectal cancer: updated overall survival analyses of the open-label, non-inferiority, randomised phase III: SOFT study,” ESMO Open, vol. 2, no. 1, article e000135, 2017. [4] T. Watanabe, Japanese Society for Cancer of the Colon, K. M. Rectum et al., “Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorec- tal cancer,” International Journal of Clinical Oncology, vol. 23, no. 1, pp. 1–34, 2018. [5] A. B. Benson 3rd, A. P. Venook, L. Cederquist et al., “Colon cancer, version 1.2017, NCCN clinical practice guidelines in oncology,” Journal of the National Comprehensive Cancer Network, vol. 15, no. 3, pp. 370–398, 2017. 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Case Reports in Oncological Medicine – Hindawi Publishing Corporation

Published: Jun 23, 2020

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