Less Common Chemotherapy Regimes

These chemotherapy regimes were identified from this CCF Forum post

Abbreviations:


 * CR - Complete Reponse indicating 100% shrinkage of tumor


 * PR - Partial Response indicating 30% or more shrinkage


 * PD - Progressive Disease indicating 20% or greater growth


 * SD - Stable Disease (not enough change for PR or PD)


 * OR - Overall Response rate (CR + PR + SD)

Regimes

1. Gemcitabine + 5FU


 * Overall response 33% in 9pts,(Murad 2003); 9.5% in 42pts,(Jacobson D -ASCO 2003); 19% in 26 pts,(Hsu C,et al-ASCO 2003).

2. Gemcitabine + Carboplatin:


 * one Study 30% of 13 pts(at ASCO 2003).

3. ECF Epirubicin + cisplatin + infusional continuous 5-FU pump


 * In a small trial of 32pt including 7 liver cancer pt;the objective response rate was 40%;and associated with less acute toxicity. However using Xeloda to substitute for 5FU continuous treatment,similar result of 40 % was also achieved but the grade 3 and 4 neutropenia(serious low WBC count) and mucositis were the major side effects;Additional phase III trial,however indicated a lower OR around 19%  but associated with less toxicity.

4. Capecitabine + mitomycin


 * regimen had a higher response rate than gemcitabine + mitomycin (31% vs 20%).

5. Infusional 5FU + cisplatin


 * one study of 25 patients, PD=24%;


 * a second study of 29 patients, the OR is 34%.

6. Gemcitabine + irinotecan


 * pt pop=16 with only 6 were CCA and the rest were gallbladder. There were 2 complete response and 6 stable response; grade 3-4 myelosuppression(50%) and thrombocytopenia (low platelet count) (28% of the patient population)

7.Capecitbine + oxaliplatin


 * (CAPOX);had overall 16 % response rate and a large number of patients had stable reponse;in another study(CCA patient pop=65;) In EXTRAhepatic CCA(ECCA) there were 2 complete and 8 partial responses as compare to NO complete or partial responses for the INTRAhepatic CCA(ICCA)patients;grade 3-4 peripheral neuropathy and 2 had allergic reaction to oxaliplatin.Somehow, for unknown reasons capecitabine works better for ECCA than ICCA and has a higher overall response rate for gallbladder cancer than cholangiocarcinoma.


 * Comparison of CAPOX with GemCIS

8. Erlotinib + bevacizumab


 * Pt pop=53, 43 had CCA the rest were gallbaladder; 9 had partial response and 51 patients had stable responses. grade 3-4 cerebral thrombosis or low blood flow(ischemia)and rash.

9. GEMOX + bevacizumab (Avastin)


 * Pt pop=35 ;CCA=25 and 10 were gallbladder. 41% had partial responses  grade 3-4 toxicity was hypertension, proteinuria, thrombosis (blood clot) cardiac ischemia and not relate to this study but later FDA gives a black box warning of 2% chance for developing of colon perforation from Avastin.

10. GEMOX + cetuximab


 * Pt pop=30 with 27 CCA patient and 3 gallbladder. 19 patients had objective responses (63% of the pop); 3 had complete response(tumor was gone) and 9 patients of the study had enough shrinkage to permit resection later. BUT the review board since long term outcome of this study was not known, therefore further study of this combination is warranted.


 * Update: during the  ASCO poster session in June,2012 the poster presenter of the final analysis of a randomized phase II "Bingle trial" indicated that GEMOX+cetuximab is NO more effective than GEMOX regimen alone.

11. 5FU continuous infusion daily for 5 days + cisplatin


 * Pop = 25 pt. --  24 % had PR ;


 * Another study (pop-29pt) indicated there were 34% partial response.

12. Gemcitabine+ irinotecan + Panitumumab


 * (7 Kras mutant pts) had a 34% response rate and OS(overall survival)=12.7months  (Gruenbergere,et al. The Lancet Oncology vol 11, issue 12, Pages 1142-1148.)-from 6/2012 ASCO.

13. GEMOX + erlotinib


 * In 268 patients studied using erlotinib 100mg daily, the OR is 30% vs 16 % who are only on GEMOX regimen ; grade 3 and 4 toxicities were uncommon in both groups. But more patients needed  dose adjustment for toxicities in the erlotinib group.. (64 vs 43%)

14. FOLFIRI = 5FU + leucovarian + irinotecan


 * Study of effectiveness as a 2nd+ line therapy.

15.Trastuzumab (Herceptin) + paclitaxel


 * 1 patient. study for metastatic CCA who has HER2/neu amplification by FISH analysis; patient experienced  dramatic response after 9 weeks of treatment. Patient had not responded to GEM/CIS; GEMCAP and  GEMOX prior to the new regimen.

16. Clinical trial on FOLFIRI + Cetuximab


 * still on trial, results may not have been reported please check the links below.


 * http://www.ncbi.nlm.nih.gov/pubmed/20164661


 * http://www.ncbi.nlm.nih.gov/pubmed/17551313


 * http://www.springerlink.com/content/b201535t2700r972/

17. EGFR/VEGF  panitumumab + bevacizumab ; erlotinib+ bevacizumab. And Sorafenib + Erlotinib


 * A recent case report of dual therapy with panitumumab and bevacizumab in a patient with widely metastatic GBC unfit for any cytotoxic therapy demonstrated a significant PR and improvement in performance status for 7 months (Riley and Carloss, 2011). A phase II study of 49 evaluable patients with chemotherapy-naïve aBTC investigated EGFR/VEGF inhibition with erlotinib and bevacizumab (Lubner et al., 2010). Six confirmed PRs were noted with a median duration of response being 8.4 months in those patients. Overall mTTP was 4.4 months and mOS was 9.9 months. Exploratory analysis of EGFR mutational status showed that those with EGFR truncation variant III or those with KRAS mutation suggested a less likely response to erlotinib; serum VEGF expression was not noted to change from baseline between responders and nonresponders. Recently, the SWOG 0941 trial enrolled 30 evaluable patients to receive first-line therapy with daily sorafenib and erlotinib with primary endpoint to improve PFS from 4 to 8 months (El-Khoueiry et al., 2012b). Two patients had a PR and 8 had SD as their best response, but there were 3 deaths while on study with one possibly related to treatment. The mPFS/OS was 2 and 6 months and the trial was stopped early due to a weak efficacy signal. Further studies are required to assess whether there may be benefit in certain subsets of patients.

18. Gencitabine + Abraxane:


 * Celgene took an interesting approach when it used Bristol Myers-Squibb's drug, Taxol in a nanoparticle formulation with albumin (this Taxol formulation is known as Abraxane) in combination with gemcitabine to improve upon the survival rates of gemcitabine alone. In those trials, where the gemcitabine-Abraxane combination was compared head to head with gemcitabine alone, Celgene only saw an increase of 1.8 months in median survival time and  about a 58% increase in the one-year survival rate for patients treated with the combination of Abraxane plus gemcitabine when compared to gemcitabine alone.

19. Gemcitabine + cetuximab:


 * http://www.cholangiocarcinoma.org/punbb … p?id=10549

20. Taxol + Zolinza (veronistat)


 * veronistat is a histone deacetylase inhibitor. Side effects included hyperglycemia(5%); Pulmonary embolism and deep vein thrombosis total (5%)


 * http://www.drugs.com/zolinza.html