Assessment of Effectiveness and Adverse Effect of New Combination Chemotherapy (irinotecan, cisplatin, and dexamethasone) in Relapse and Refractory Hodgkin Lymphoma.

Background: Chemotherapy with Adriamycin, Bleomycin, Vinblastine, and Dacarbazine (ABVD regimen) cannot cure all patients with Hodgkin lymphoma. In this study, we evaluated the efficacy and adverse effect of a new regimen consist Irinotecan, Cisplatin, and Dexamethasone (ICD) in relapsed and refractory Hodgkin lymphoma as the second to fifth line of treatment. Materials and Methods: We performed a retrospective study in 26 relapsed or refractory patients with Hodgkin lymphoma receiving at least the first-line chemotherapy regimen (ABVD) and (ICD) as salvage therapy in Thaleghany Hospital from 2012 to 2018. This regimen consisted of Irinotecan 65mg/m2 D1, D8, Cisplatin 30mg/m2 D1, D8, and dexamethasone 40mg D1, 2, 8, and 9 was administered every 3 weeks for 6 cycles.  Treatment was discontinued in cases of disease progression or severe toxicity. Response to treatment was evaluated after two cycles. Patients with complete and partial remission were candidates for high-dose chemotherapy and autologous stem cell transplantation. Twenty-four patients were enrolled in the study. The mean age of 22 patients was 31.5 (19-67) years. Seven patients (29.1%) were in the first recurrence, and 17 (70.8%) were in the second or subsequent recurrence. Results: According to this study, three patients (12.5%) had complete response, 13 (45%) had partial response, four (16.6%) had stable disease, and four (16.6%) had progressive disease. Nine patients (37.5%) received high-dose chemotherapy and autologous stem cell support after ICD regimen. None of the cycles of chemotherapy were delayed due to treatment-related adverse event. Overall survival after six months in all patients was 91%, and mortality rate was 8.3% at the end of the study. Conclusion: The goal of salvage chemotherapy in relapsed or refractory Hodgkin Lymphoma is achieving CR or PR preparation patients for stabilization with BMT. Thus, we recommend ICD as one of the most effective protocols with overall response rate of 66% in this population.

Comparing efficacy and safety of P013, a proposed pertuzumab biosimilar, with the reference product in HER2-positive breast cancer patients: a randomized, phase III, equivalency clinical trial.

BACKGROUND: Breast cancer is the most frequently diagnosed cancer and the leading reason for cancer-related death among women. Neoadjuvant treatment with dual-HER2 (human epidermal growth factor receptor 2) blockade has shown promising effects in this regard. The present study aimed to compare the efficacy and safety of a proposed pertuzumab biosimilar with the reference pertuzumab. METHODS: This randomized, phase III, multicenter, equivalency clinical trial was conducted on chemotherapy-naive women with HER2-positive breast cancer. Patients were randomly assigned (1:1) to receive six cycles of either P013 (CinnaGen, Iran) or the originator product (Perjeta, Roche, Switzerland) along with trastuzumab, carboplatin, and docetaxel every 3 weeks. Patients were stratified by cancer type (operable, locally advanced, inflammatory) and hormone receptor status. The primary endpoint was breast pathologic complete response (bpCR). Secondary endpoints included comparisons of total pCR, overall response rate (ORR), breast-conserving surgery (BCS), safety, and immunogenicity. RESULTS: Two hundred fourteen patients were randomized to treatment groups. bpCR rate in the per-protocol population was 67.62% in the P013 and 71.57% in the reference drug groups. Based on bpCR, P013 was equivalent to the reference pertuzumab with a mean difference of - 0.04 (95% CI: - 0.16, 0.09). Secondary endpoints were also comparable between the two groups. CONCLUSIONS: The proposed biosimilar P013 was equivalent to the reference product in terms of efficacy. The safety of both medications was also comparable.

A Cross-Sectional Study for Evaluation of KRAS and BRAF Mutations by Reverse Dot Blot, PCR-RFLP, and Allele-Specific PCR Methods Among Patients with Colorectal Cancer.

BACKGROUND: KRAS and BRAF genes are the biomarkers in Colorectal Cancer (CRC) which play prognostic and predictive roles in CRC treatment. Nowadays, the selection of rapid and available methods for studying KRAS and BRAF mutations in anti-EGFR therapy of patients suffering from CRC plays a significant role. In this study, the mutations of these two oncogenes were evaluated by different methods. METHODS: This study was performed on 50 Formalin-Fixed Paraffin-Embedded (FFPE) tissue blocks of patients diagnosed with colorectal cancer. After DNA extraction, KRAS and BRAF gene mutations were evaluated using reverse dot blot, and results were compared with PCR-RFLP and allele-specific PCR for KRAS and BRAF mutations, respectively. RESULTS: KRAS gene mutations were detected in 42% of patients, of which 30% were in codon 12 region, and 12% in codon 13. The most frequent mutations of KRAS were related to G12D and 10% of patients had BRAF mutated genes. The type of KRAS gene mutations could be evaluated by reverse dot blot method. In general, the results of PCR-RFLP and allele-specific PCR were similar to the findings by reverse dot blot method. CONCLUSION: These findings suggest that PCR-RFLP and allele-specific PCR methods are suitable for screening the presence of the mutations in KRAS and BRAF oncogenes. In fact, another method with more sensitivity is needed for a more accurate assessment to determine the type of mutations. Due to higher speed of detection, reduced Turnaround Time (TAT), and possible role of some KRAS point mutations in overall survival, reverse dot blot analysis seems to be an optimal method.

Efficacy of Adding Bortezomib to Salvage Chemotherapy in Relapsed/refractory Acute Myeloid Leukemia a Prospective Non-Interventional Study.

Relapsed/refractory acute myeloid leukemia (RR-AML) are important types of hematological malignancy for which no effective salvage chemotherapy has been approved. The main purpose of this study was to determine the effectiveness of adding Bortezomib to salvage chemotherapy protocol in RR-AML patients. In this prospective non-interventional study, 40 consecutive patients with RR-AML attending Taleghani Hospital who underwent salvage therapy, were enrolled and subdivided into salvage chemotherapy plus Bortezomib and salvage chemotherapy without Bortezomib and the therapeutic response, adverse effects, and survival among them were determined. The results in this study demonstrated that complete response was present in 30% and 25% in Bortezomib group and the other group, respectively and the partial response was seen in 35% and 50% and no response was present in 35% and 25%, respectively (P = 0.621). Furthermore, in each group, 15% had a side effect (P = 1.000). Mean survival was 8.2 and 7.1 in Bortezomib and the other group, respectively (P = 0.275). Based on the obtained results, it may be concluded that adding Bortezomib to salvage chemotherapy is feasible in RR-AML patients. For evaluation of efficacy further study is recommended.

Adding Oral Pioglitazone to Standard Induction Chemotherapy of Acute Myeloid Leukemia: A Randomized Clinical Trial.

BACKGROUND: The hypothesis of an effect by thiazolidinedione on leukemia cells was proposed 2 decades ago, but there is little clinical evidence regarding its efficacy. We evaluated the safety and efficacy of adding pioglitazone to standard induction chemotherapy in patients with acute myeloid leukemia (AML). PATIENTS AND METHODS: In this randomized clinical trial, newly diagnosed AML patients were randomized to 1 of 2 groups. Patients in both groups received cytarabine (100 mg/m2 per day for 7 days) and daunorubicin (60 mg/m2 per day for 3 days). Patients in the pioglitazone group additionally received oral pioglitazone (45 mg per day). The 2 groups were compared according to remission rate, laboratory findings, and adverse events during treatment. RESULTS: Forty patients were evaluated, 20 patients in each group. The complete remission rate was 20% more in the pioglitazone group compared to the control group (P = .202). Complications due to pioglitazone discontinuation were observed in 2 cases. The mean serum alanine aminotransferase in the fourth treatment week was significantly more in pioglitazone group compared to the control group (65.5 vs. 33.6 mg/dL, P = .039). The mean serum creatinine in all treatment phases was significantly higher in the pioglitazone group compared to the control group (P < .05). There were no significant differences between the 2 groups regarding other laboratory findings (P > .05). CONCLUSION: Adding pioglitazone to cytarabine and daunorubicin increased the remission rate in AML patients compared to control subjects. Although this difference in remission rate between the 2 groups was not statistically significant, it could be important in the clinical setting. Pioglitazone may provide benefits as an adjuvant therapy for AML patients without causing serious adverse events.

Prophylaxis of neutropenic fever with ciprofloxacin in patients with acute myeloid leukemia treated with intensive chemotherapy.

AIMS: Neutropenic fever is one of the most serious complications after induction chemotherapy in acute myeloid leukemia (AML). Prophylaxis with antibiotics for prevention of neutropenic fever in AML is controversial and there are few studies on this issue from developing countries. METHODS: In this retrospective study, we analyzed the clinical data and outcome of patients with AML who did or did not receive prophylactic ciprofloxacin 500 mg BD for neutropenic fever. RESULTS: A total of 69 AML patients were treated by "3 + 7" protocol for their first induction chemotherapy. Prophylaxis was given to 25 of them. Incidence of neutropenic fever was the same in both groups (80% vs 82%). Duration of fever and the mortality rate were also similar in both groups. CONCLUSION: It seems that in developing countries, using prophylactic ciprofloxacin has no significant effect on the incidence of neutropenic fever and the outcome of the AML patients.

Modified Irinotecan Plus Cisplatin and Dexamethasone (ICD) Combination Chemotherapy as Salvage Chemotherapy for Patients with Relapsed/Refractory Diffuse Large Cell Lymphoma.

About 50 % of patients with diffuse large cell lymphoma are candidate for salvage chemotherapy followed by bone marrow transplantation in the selected patients. In the current study we evaluated modified ICD (Irinotecan, Cisplatin, and Dexamethasone with G-CSF support) as salvage chemotherapy in the patients previously treated with R-CHOP or CHOP. In a retrospective study we evaluated 16 patients treated with modified ICD: irinotecan 65 mg/m(2) (max 100 mg)/day plus cisplatin 30 mg/m(2) (max 50 mg)/day and dexamethasone 40 mg/day on days 1 and 8. Prednisolone 200 mg divided in 2 doses was given orally on days 2 and 9. G-CSF (PDgrastim) was administered at 300 µg/day subcutaneously on days 4-6 and 11-13. pre- and post-hydration was given according to our hospital protocol. Overall response rate was 75 % for all of the patients and 90 % for the patients treated as first line salvage. The median overall survival was 23 ± 12 months. There was no grade 3/4 of neutropenia and no cycles of chemotherapy were delayed due to leucopenia. Modified ICD might be an effective salvage regimen for refractory/relapsed lymphoma patients. Unlike original ICD, leucopenia does not seem to be a limiting factor. So we conclude that modified ICD shall be considered as a safe and effective regimen for salvage chemotherapy in refractory/relapsed patients.

Primary pulmonary plasmacytoma with diffuse alveolar consolidation: a case report.

Solitary extramedullary plasmacytomas are plasma cell tumors that tend to develop in mucosa-associated lymphoid tissues including the sinonasal or nasopharyngeal regions. Primary plasmacytoma of the lung is exceedingly rare and often presents as a solitary mass or nodule in mid-lung or hilar areas and diagnosed after resection. Herein, we report a case of primary pulmonary plasmacytoma that presented with diffuse alveolar consolidation and diagnosed by transbronchial lung biopsy.