Chemotherapy after immunotherapy failure in patients with advanced gastrointestinal tumors

Argota, I. Baraibar; Romano, P. Martin; Sanmamed, Miguel F.; Ruíz, Mario Castaño; Melero, Ignacio; Resano, L.; Ortega, A; Ponz-Sarvisé, Mariano; Álvarez, E. Castañón

doi:10.1093/annonc/mdy314.002

Cited by 3 publications

(2 citation statements)

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“…Since 2020, when individual baseline PBTs are severely unfavorable, ad hoc exploratory practice includes both early recognition of relapse or impending crises, and addition of docetaxel and mitomycin (DM), with or without targeted therapy, to increase the chances of rapid response. Also, our anecdotal findings and independent work have produced long lasting response with the combinations of GFLIO-DM or single drugs, respectively, after failure of both the individual treatments with chemotherapy and immunotherapy ( 32 – 34 , 47 , 48 ). However, the patients in this series did not receive immunotherapy.…”

Section: Discussionmentioning

confidence: 77%

Cholangiocarcinoma, sequential chemotherapy, and prognostic tests

Bruckner,

De Jager,

Knopf

et al. 2024

Front. Oncol.

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IntroductionRoutine blood tests are prognostic tests for patients with cholangiocarcinoma. New drug regimens may produce a median overall survival of 2 years or more.MethodsThis single practice, IRB-approved, phase II trial examines prognostic tests, Kaplan-Meier survival, and univariate Cox regression analyses. Eligibility requires: intent-to-treat; signed consent; advanced measurable intrahepatic cholangiocarcinoma, with or without resistance to the test drugs; any adult age; performance status 0–2; and expected survival of ≥ 6 weeks. Biweekly treatment, with 1/3 of standard dosages in mg/M2, includes: Gemcitabine 500; 5-Fluorouracil 1200 over 24 hours; Leucovorin 180; Irinotecan 80; and on day 2, Oxaliplatin 40. On progression, drugs are added on day 2: first, Docetaxel 25 precedes Oxaliplatin, with or without Mitomycin C 6 after Oxaliplatin. The next sequential additions are day 1, Cetuximab 400 total mg, then 200 mg weekly, and then Bevacizumab 10 mg/kg is substituted for Cetuximab (FDA IND# 119005).ResultsFor 35 patients, 19 with 1–2 lines of prior therapy, resistant tumors, and 16 no prior therapy, survival at 24-months is ≥ 72 and ≥ 58%, respectively. For 14 patients aged ≥ 70 years, ≥ 63% survive 24 months, P = 0.28. Validated tests that predict ≤ 6-month survivals find median survival times of 17-months through > 2-years when compared to patients with favorable tests: Neutrophils lymphocyte ratio > 3.0, HR = 6.54, P < 6.4x10–3; absolute neutrophil count > 8000/μl, HR = 4.95, P < 6.5x10–3; serum albumin < 3.5 g/dl, HR = 4.10, P < 0.03; and lymphocyte monocyte ratio< 2.1, HR = 1.6, P = 0.50. Overall, the 76 (60–90)% of patients with 0–2 out of 4 high risk tests survive ≥ 24 months, (P = 7.1x10–3). Treatments produce neither hospitalization, neutropenic fever, severe enteritis, nor severe neuropathies.ConclusionTwo-year survival is replicable and predictable. Findings warrant phase III validation tests of sequential regimens, re-challenge with recombination, low dosages, and blood tests that are associated with lethal mechanisms that impair response and survival.

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Section: Discussionmentioning

confidence: 77%

Cholangiocarcinoma, sequential chemotherapy, and prognostic tests

Bruckner,

De Jager,

Knopf

et al. 2024

Front. Oncol.

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“…This is in a patient with prior exposure to carboplatin, paclitaxel as well as 5‐FU/mitomycin upfront chemotherapy. The dramatic response may be secondary to prior exposure to immunotherapy, which is increasingly being reported across multiple tumor types where the sequence of immunotherapy followed by chemotherapy is yielding greater than historical responses as summarized in Table .…”

Section: Introductionmentioning

confidence: 99%

Dramatic response to modified docetaxel, cisplatin, and fluorouracil chemotherapy after immunotherapy in a patient with refractory metastatic anal cancer

Shahjehan

Kamatham

Ritter

et al. 2019

Clinical Case Reports

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Doublet chemotherapies are the mainstay in the management of metastatic anal cancer. Immunotherapy has been incorporated into guidelines in a refractory setting. Treatment options remain limited with tumor progression beyond immunotherapy. Modified docetaxel, cisplatin, and fluorouracil (mDCF) chemotherapy, after progression postimmunotherapy, has shown a near‐complete response in our patient with metastatic anal cancer. This likely is secondary to the sequence of immunotherapy followed by chemotherapy that is yielding greater than historical responses.

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Actionable tests and treatments for patients with gastrointestinal cancers and historically short median survival times

et al. 2022

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Background Patients have difficult unmet needs when standard chemotherapy produces a median survival of less than 1 year or many patients will experience severe toxicities. Blood tests can predict their survival. Methods Analyses evaluate predictive blood tests to identify patients who often survive 1 and 2 years. A four-test model includes: albumin, absolute neutrophil count, neutrophil-lymphocyte ratio, and lymphocyte-monocyte ratio. Individual tests include: alkaline phosphatase, lymphocytes, white blood count, platelet count, and hemoglobin. Eligible patients have advanced: resistant 3rd line colorectal, and both resistant and new pancreatic and intrahepatic bile duct cancers. Eligibility characteristics include: biopsy-proven, measurable metastatic disease, NCI grade 0–2 blood tests, Karnofsky Score 100–50, and any adult age. Drugs are given at 1/4–1/3 of their standard dosages biweekly: gemcitabine, irinotecan, fluorouracil, leucovorin, and day 2 oxaliplatin every 2 weeks. In case of progression, Docetaxel is added (except colon cancer), with or without Mitomycin C, and next cetuximab (except pancreatic and KRAS BRAF mutation cancers). Bevacizumab is substituted for cetuximab in case of another progression or ineligibility. Consent was written and conforms with Helsinki, IRB, and FDA criteria (FDA #119005). Results Median survival is 14.5 months. Of 205 patients, 60% survive 12, and 37% survive 24 months (95% CI ± 8%). Survival is > 24, 13, and 3.8 months for patients with 0, 1–2, and 3–4 unfavorable tests, respectively. Individual “favorable and unfavorable” tests predict long and short survival. Neither age nor prior therapy discernibly affects survival. Net rates of clinically significant toxicities are less than 5%. Conclusion Treatments reproduce predictable, greater than 12 and 24-month chances of survival for the aged and for patients with drug-resistant tumors. Evaluation of blood tests may change practice, expand eligibility, and personalize treatments. Findings support investigation of drug combinations and novel dosages to reverse resistance and improve safety.

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Chemotherapy after immunotherapy failure in patients with advanced gastrointestinal tumors

Cited by 3 publications

References 0 publications

Cholangiocarcinoma, sequential chemotherapy, and prognostic tests

Cholangiocarcinoma, sequential chemotherapy, and prognostic tests

Dramatic response to modified docetaxel, cisplatin, and fluorouracil chemotherapy after immunotherapy in a patient with refractory metastatic anal cancer

Actionable tests and treatments for patients with gastrointestinal cancers and historically short median survival times

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