Cis-platin based combination chemotherapy for advanced ovarian cancer. High overall response rate with curative potential only in women with small tumor burdens

PURPOSE This study aimed to evaluate the activity and toxicity of carboplatin (PPL) and ifosfamide (IFO) in patients with epithelial ovarian cancer previously treated with cisplatin (CDDP)-containing regimens. PATIENTS AND METHODS From July 1989 to December 1991, 35 patients with epithelial ovarian cancer relapsed or refractory to CDDP as first-line chemotherapy were treated. PPL was administered at a dose of 300 mg/m2 intravenously (IV) on day 1 and IFO at a dose of 1,500 mg/m2 IV on days 1 to 3 every 3 to 4 weeks. Criteria for evaluating previous response to CDDP were strictly defined. RESULTS The overall response rate was 43% (complete response [CR], 6%; partial response [PR], 37%) and the median duration of response was 7 months (range, 3 to 16). In potentially platinum-sensitive (PPS; relapsed) patients, the overall response rate was 56%. None of the primary platinum-resistant (PPR) patients obtained a clinical response to PPL plus IFO, whereas one of five secondary platinum-resistant (SPR) patients obtained a PR. The regimen was easily manageable. CONCLUSION PPL plus IFO is useful and well-tolerated combination in salvage treatment of patients with advanced ovarian cancer. However, clear synergism between PPL and IFO that could overcome intrinsic or acquired CDDP resistance was not observed. The advantage of PPL plus IFO as compared with CDDP-containing regimens is represented by the increased tolerability and the reduced neurotoxicity, nephrotoxicity, and ototoxicity as compared with CDDP-containing regimens. It is essential that the patient population be defined according to their previous response to platinum therapy in trials involving second-line therapy of ovarian cancer.

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Safety, immunogenicity, and clinical efficacy of durvalumab in combination with folate receptor alpha vaccine TPIV200 in patients with advanced ovarian cancer: a phase II trial

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-000829 ◽

2020 ◽

Vol 8 (1) ◽

pp. e000829 ◽

Cited By ~ 1

Author(s):

Dmitriy Zamarin ◽

Sven Walderich ◽

Aliya Holland ◽

Qin Zhou ◽

Alexia E Iasonos ◽

...

Keyword(s):

Ovarian Cancer ◽

T Cell ◽

Phase Ii ◽

Clinical Benefit ◽

Overall Response Rate ◽

Response Rate ◽

Phase Ii Trial ◽

Folate Receptor ◽

Advanced Ovarian Cancer ◽

Cell Responses

BackgroundImmune checkpoint inhibitors (ICIs) to date have demonstrated limited activity in advanced ovarian cancer (OC). Folate receptor alpha (FRα) is overexpressed in the majority of OCs and presents an attractive target for a combination immunotherapy to potentially overcome resistance to ICI in OCs. The current study sought to examine clinical and immunologic responses to TPIV200, a multiepitope FRα vaccine administered with programmed death ligand 1 (PD-L1) inhibitor durvalumab in patients with advanced platinum-resistant OC.MethodsFollowing Simon two-stage phase II trial design, 27 patients were enrolled. Treatment was administered in 28-day cycles (intradermal TPIV200 and granulocyte-macrophage colony-stimulating factor (GM-CSF) for 6 cycles and intravenous durvalumab for 12 cycles). Primary endpoints included overall response rate and progression-free survival at 24 weeks. Translational parameters focused on tumor microenvironment, PD-L1 and FRα expression, and peripheral vaccine-specific immune responses.ResultsTreatment was well tolerated, with related grade 3 toxicity rate of 18.5%. Increased T cell responses to the majority of peptides were observed in all patients at 6 weeks (p<0.0001). There was one unconfirmed partial response (3.7%) and nine patients had stable disease (33.3%). Clinical benefit was not associated with baseline FRα or PD-L1 expression. One patient with prolonged clinical benefit demonstrated loss of FRα expression and upregulation of PD-L1 in a progressing lesion. Despite the low overall response rate, the median overall survival was 21 months (13.5–∞), with evidence of benefit from postimmunotherapy regimens.ConclusionsCombination of TPIV200 and durvalumab was safe and elicited robust FRα-specific T cell responses in all patients. Unexpectedly durable survival in this heavily pretreated population highlights the need to investigate the impact of FRα vaccination on the OC biology post-treatment.

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5-Fluorouracil, Vincristine and Hydroxyurea Combination Chemotherapy in Metastatic Colorectal Cancer

Tumori Journal ◽

10.1177/030089168306900519 ◽

1983 ◽

Vol 69 (5) ◽

pp. 485-487 ◽

Cited By ~ 3

Author(s):

Anna Marina Liberati ◽

Francesco Di Costanzo ◽

Franco Buzzi ◽

Giuseppe Fatati ◽

Bruno Biscottini ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Metastatic Colorectal Cancer ◽

Combination Chemotherapy ◽

Stable Disease ◽

Overall Response Rate ◽

Response Rate ◽

Drug Regimen ◽

Overall Response ◽

Tumor Remission

Twenty consecutive patients who had biopsy proven metastatic colorectal cancer were treated with combination chemotherapy. The drug regimen (FVH), in a 4 week cycle, consisted of 5-fluorouracil (600 mg/m2 i.v. on days 1, 8, 15 and 22), vincristine (1.4 mg/m2 i.v. on day 4), and hydroxyurea (2400 mg/m2 p.o. on days 3, 10, 17 and 24). Three of the 18 evaluable patients achieved an objective tumor remission (2 CR and 1 PR) and 15 patients had stable disease. The overall response rate to FVH was therefore not superior to that achieved in patients who received 5-fluorouracil alone, and the overall survival in this study was comparable to that of other studies involving patients with metastatic colorectal cancer.

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Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA)

Journal of Clinical Oncology ◽

10.1200/jco.21.00334 ◽

2021 ◽

pp. JCO.21.00334

Author(s):

Junzo Hamanishi ◽

Nobuhiro Takeshima ◽

Noriyuki Katsumata ◽

Kimio Ushijima ◽

Tadashi Kimura ◽

...

Keyword(s):

Ovarian Cancer ◽

Liposomal Doxorubicin ◽

Overall Response Rate ◽

Response Rate ◽

Pegylated Liposomal Doxorubicin ◽

Hazard Ratio ◽

Open Label ◽

Overall Response ◽

Platinum Resistant ◽

Duration Of Response

PURPOSE This phase III, multicenter, randomized, open-label study investigated the efficacy and safety of nivolumab versus chemotherapy (gemcitabine [GEM] or pegylated liposomal doxorubicin [PLD]) in patients with platinum-resistant ovarian cancer. MATERIALS AND METHODS Eligible patients had platinum-resistant epithelial ovarian cancer, received ≤ 1 regimen after diagnosis of resistance, and had an Eastern Cooperative Oncology Group performance score of ≤ 1. Patients were randomly assigned 1:1 to nivolumab (240 mg once every 2 weeks [as one cycle]) or chemotherapy (GEM 1000 mg/m2 for 30 minutes [once on days 1, 8, and 15] followed by a week's rest [as one cycle], or PLD 50 mg/m2 once every 4 weeks [as one cycle]). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate, duration of response, and safety. RESULTS Patients (n = 316) were randomly assigned to nivolumab (n = 157) or GEM or PLD (n = 159) between October 2015 and December 2017. Median OS was 10.1 (95% CI, 8.3 to 14.1) and 12.1 (95% CI, 9.3 to 15.3) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.0; 95% CI, 0.8 to 1.3; P = .808). Median PFS was 2.0 (95% CI, 1.9 to 2.2) and 3.8 (95% CI, 3.6 to 4.2) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.5; 95% CI, 1.2 to 1.9; P = .002). There was no statistical difference in overall response rate between groups (7.6% v 13.2%; odds ratio, 0.6; 95% CI, 0.2 to 1.3; P = .191). Median duration of response was numerically longer with nivolumab than GEM or PLD (18.7 v 7.4 months). Fewer treatment-related adverse events were observed with nivolumab versus GEM or PLD (61.5% v 98.1%), with no additional or new safety risks. CONCLUSION Although well-tolerated, nivolumab did not improve OS and showed worse PFS compared with GEM or PLD in patients with platinum-resistant ovarian cancer.

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Cisplatin in the treatment of recurrent childhood primary brain tumors.

Journal of Clinical Oncology ◽

10.1200/jco.1988.6.1.62 ◽

1988 ◽

Vol 6 (1) ◽

pp. 62-66 ◽

Cited By ~ 89

Author(s):

R W Walker ◽

J C Allen

Keyword(s):

Brain Tumors ◽

Germ Cell ◽

Germ Cell Tumor ◽

Overall Response Rate ◽

Response Rate ◽

Cell Tumor ◽

Primitive Neuroectodermal Tumors ◽

Primary Brain Tumors ◽

Overall Response ◽

Neuroectodermal Tumors

Thirty-three patients were treated with intravenous (IV) cisplatin (CPDD) of whom 32 were considered evaluable. There were 14 medulloblastomas, five primitive neuroectodermal tumors (PNET), nine gliomas, three ependymomas, and one germ cell tumor. The overall response rate was 13 of 32 (41%). Eleven responses (five complete [CR], five partial [PR], one mixed [MR]) were noted in the patients with medulloblastoma. The response rate within this group was 79%. Toxicity was tolerable, although it precluded further therapy in five patients.

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Efficacy of Repetitive Transcranial Magnetic Stimulation (rTMS) for Tinnitus: A Retrospective Study

Ear Nose & Throat Journal ◽

10.1177/01455613211016896 ◽

2021 ◽

pp. 014556132110168

Author(s):

Haidi Yang ◽

Gui Cheng ◽

Zhengrong Liang ◽

Wenting Deng ◽

Xiayin Huang ◽

...

Keyword(s):

Transcranial Magnetic Stimulation ◽

Magnetic Stimulation ◽

Overall Response Rate ◽

Response Rate ◽

Repetitive Transcranial Magnetic Stimulation ◽

Subjective Assessment ◽

Overall Response ◽

Duration Of Disease ◽

Vas Scores ◽

Assessment Result

Objective: Current studies still find insufficient evidence to support the routine use of repetitive transcranial magnetic stimulation (rTMS) in tinnitus. This study aimed to assess response of tinnitus to treatment with rTMS and identify factors influencing the overall response. Methods: Between January 2016 and May 2017, 199 tinnitus patients were identified from a retrospective review of the electronic patient record at the Sun Yat-sen Memorial Hospital. All patients received rTMS treatment. Their clinicodemographic profile and outcomes, including the tinnitus handicap inventory (THI) and visual analog scale (VAS) scores, were extracted for analysis. Results: Regarding the THI results, 62.3% of all patients responded to rTMS. The analysis of the VAS score revealed an overall response rate of 66.3%. Both percentages were close to the patient’s subjective assessment result, of 63.8%. Patients with tinnitus of less than 1-week duration had the highest response rate to rTMS in terms of either THI/VAS scores or the patient’s subjective assessment of symptoms. Tinnitus duration was recognized as a factor influencing the overall response to the treatment. Conclusions: Repetitive transcranial magnetic stimulation treatment is effective for patients with tinnitus, but its efficacy is affected by tinnitus duration. Tinnitus patients are advised to attend for rTMS as soon as possible since therapy was more effective in those with a shorter duration of disease of less than 1 week.

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Combination of trastuzumab, pertuzumab and docetaxel in patients with advanced non-small cell lung cancer (NSCLC) harboring HER2 mutation: Final results from the IFCT-1703 R2D2 trial.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.9015 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 9015-9015

Author(s):

Julien Mazieres ◽

Claire Lafitte ◽

Charles Ricordel ◽

Laurent Greillier ◽

Jean-Louis Pujol ◽

...

Keyword(s):

Brain Metastases ◽

Overall Response Rate ◽

Advanced Nsclc ◽

Response Rate ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Loading Dose ◽

Overall Response ◽

Grade 3 ◽

Exon 20

9015 Background: Human epidermal growth factor receptor 2 ( HER2) exon 20 insertions and mutations are oncogenic drivers found in 1-2% of NSCLC. However, there are no approved therapies for these patients. Many studies suggest that the use of HER2 inhibitors developed for breast cancer patients might be of interest in this setting. The aim of this trial was to prospectively evaluate the interest of a combination of two antibodies against HER2 (trastuzumab and pertuzumab) with docetaxel. Methods: IFCT-1703 R2D2 trial is a multicenter, non-randomized phase 2 study with a two-stage design, a power of 90% and an alpha risk at 5% (one-sided). HER2 mutational status was assessed locally in certified molecular genetic centers. Main other inclusion criteria were advanced NSCLC, progression after ≥ 1 platinum-based chemotherapy, asymptomatic brain metastases, left ventricular ejection fraction (LVEF) ≥ 50%, and PS 0-2. Patients were treated every 3 weeks with pertuzumab at a loading dose of 840 mg, and 420 mg thereafter; plus trastuzumab at a loading dose of 8 mg/kg and 6 mg/kg thereafter; and docetaxel at 75 mg/m². Treatment was given until toxicity or disease progression. The primary outcome was overall response rate (ORR). Other endpoints included duration of response, progression-free survival and safety. NCT number: NCT03845270. Results: From May 2019 to October 2020, 45 patients were enrolled in 17 centers and received study treatment. Median age was 64.5 years (range 31–84), 72% females, 35% smokers, 100% non-squamous histology and 15% with ECOG PS 2. 31.1% patients had brain metastases. PD-L1 was expressed ≥ 1% and ≥ 50% in 36% and 7% of the patients, respectively. No other oncogene driver was found associated with HER2 exon 20 mutation. With a median follow-up of 12 months, 44 (98%) patients were evaluable for the primary endpoint. Overall response rate was 29% (n = 13), stable disease 56% (n = 26). Median PFS was 6.8 months (95% CI[4.0-8.5]). Median duration of treatment in patients with confirmed response (n = 13) was 10 months (95% CI[2.7-14.9]). At the time of data cut-off, 15 patients (33%) were still under treatment. Grade 3/4 treatment-related adverse events (AEs) were observed in 64% of patients. No patient experienced treatment discontinuation because of toxicity. One sudden death was possibly related to treatment. Most frequent grade ≥ 3 AEs were neutropenia (33%), diarrhea (13%) and anaemia (9%). Grade 1/2 dyspnea was observed in 3 (6.7%) patients. No ILD were reported. Variation LVEF was -1.72% on average (min: -18 %; max: 10 %). Conclusions: The triplet trastuzumab, pertuzumab and docetaxel is feasible and active in HER2 pretreated advanced NSCLC. These results confirm the activity of HER2 antibodies-based strategy which should be considered in these patients. Clinical trial information: NCT03845270.

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Phase 1/2a study of 177Lu-lilotomab satetraxetan in relapsed/refractory indolent non-Hodgkin lymphoma

Blood Advances ◽

10.1182/bloodadvances.2020002583 ◽

2020 ◽

Vol 4 (17) ◽

pp. 4091-4101

Author(s):

Arne Kolstad ◽

Tim Illidge ◽

Nils Bolstad ◽

Signe Spetalen ◽

Ulf Madsbu ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Overall Response Rate ◽

Response Rate ◽

Phase 1 ◽

B Cell Lymphoma ◽

Complete Response ◽

Hematologic Toxicity ◽

Overall Response ◽

Non Hodgkin Lymphoma ◽

Anti Cd20

Abstract For patients with indolent non-Hodgkin lymphoma who fail initial anti-CD20–based immunochemotherapy or develop relapsed or refractory disease, there remains a significant unmet clinical need for new therapeutic approaches to improve outcomes and quality of life. 177Lu-lilotomab satetraxetan is a next-generation single-dose CD37-directed radioimmunotherapy (RIT) which was investigated in a phase 1/2a study in 74 patients with relapsed/refractory indolent non-Hodgkin B-cell lymphoma, including 57 patients with follicular lymphoma (FL). To improve targeting of 177Lu-lilotomab satetraxetan to tumor tissue and decrease hematologic toxicity, its administration was preceded by the anti-CD20 monoclonal antibody rituximab and the “cold” anti-CD37 antibody lilotomab. The most common adverse events (AEs) were reversible grade 3/4 neutropenia (31.6%) and thrombocytopenia (26.3%) with neutrophil and platelet count nadirs 5 to 7 weeks after RIT. The most frequent nonhematologic AE was grade 1/2 nausea (15.8%). With a single administration, the overall response rate was 61% (65% in patients with FL), including 30% complete responses. For FL with ≥2 prior therapies (n = 37), the overall response rate was 70%, including 32% complete responses. For patients with rituximab-refractory FL ≥2 prior therapies (n = 21), the overall response rate was 67%, and the complete response rate was 24%. The overall median duration of response was 13.6 months (32.0 months for patients with a complete response). 177Lu-lilotomab satetraxetan may provide a valuable alternative treatment approach in relapsed/refractory non-Hodgkin lymphoma, particularly in patients with comorbidities unsuitable for more intensive approaches. This trial was registered at www.clinicaltrials.gov as #NCT01796171.

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Phase I study of the combination of fludarabine, mitoxantrone, and dexamethasone in low-grade lymphoma.

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.3.575 ◽

1994 ◽

Vol 12 (3) ◽

pp. 575-579 ◽

Cited By ~ 69

Author(s):

P McLaughlin ◽

F B Hagemeister ◽

F Swan ◽

F Cabanillas ◽

O Pate ◽

...

Keyword(s):

Overall Response Rate ◽

Response Rate ◽

Single Agent ◽

Active Agent ◽

Large Cell ◽

Maximum Tolerated Dose ◽

Low Grade ◽

Overall Response ◽

Nonhematologic Toxicity ◽

High Fraction

PURPOSE Fludarabine is an active agent for patients with low-grade lymphoma (LGL) but has mainly been used as a single agent. This trial was designed to define the maximum-tolerated dose (MTD) of a combination of fludarabine, mitoxantrone, and dexamethasone (FND), to identify the toxicities of these agents in combination, and to make preliminary observations about the efficacy of this combination. PATIENTS AND METHODS Twenty-one patients with recurrent LGL or follicular large-cell lymphoma were treated, in cohorts of three, at stepwise escalating doses. Patients were required to have adequate marrow function and normal renal, hepatic, and cardiac function. RESULTS The MTD of the combination was found to be as follows: fludarabine, 25 mg/m2/d (days 1 to 3); mitoxantrone, 10 mg/m2 (day 1); and dexamethasone, 20 mg/d (days 1 to 5). Each course was administered monthly, and up to eight courses were given. Dose-limiting toxicities were neutropenia and infections. Thrombocytopenia was modest. Nonhematologic toxicity was very modest. Responses were seen at every dose level. The overall response rate was 71%, with a 43% complete remission (CR) rate. The median duration of CR was 18 months (with follow-up duration from 13 to 28+ months). CONCLUSION FND was well tolerated in this population. While our primary aim was to define the MTD, our preliminary observations on the efficacy of the regimen were favorable. The overall response rate was high, there was a high fraction of CRs, and our early impression is that these responses are durable.

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