Aggressive Angiomyxoma of the Lower Female Genital Tract: A Review of the MITO Rare Tumors Group.

Aggressive angiomyxoma (AAM) is a rare, locally aggressive, myxoid mesenchymal neoplasm primarily found in the pelvic and perineal regions of young adult females. It is a slow growing and locally infiltrating tumor. Preoperative diagnosis is difficult due to the rarity of these tumors and absence of characteristic signs and symptoms. The primary management is tumor excision. Incomplete excision is common because of the infiltrating nature of the neoplasm and absence of a definite capsule. Other non- surgical modalities have been employed, such as radiotherapy, embolization, GnRH analogues or other anti-estrogenic agents. Local relapses occur in 30-40% of the cases, and often appear many years (sometimes decades) after the first excision. Occasional distant metastasis has also been reported. A limited number of cases have been reported in the literature, mostly in the form of small case series or isolated case reports. Therefore, the aim of this paper by a team of experts from the MITO rare tumors group is to review clinical findings, pathologic characteristics and outcome of patients affected by this rare condition in order to be able to offer up-to-date guidance on the management of these cases.

Management of primary and recurrent Bartholin's gland carcinoma: A systematic review on behalf of MITO Rare Cancer Group.

Bartholin gland carcinoma is an extremely rare disease. Information regarding treatment is scarce and there is no strict consensus on best practice. All studies reporting cases of Bartholin's gland cancer were screened and evaluated for inclusion. Baseline characteristics of studies were extracted. A total number of 290 manuscripts collected were available for the review process. Studies included in a previous systematic review were not duplicated. In total, details of 367 patients were collected, as follows: histological features, clinical presentation, treatment, recurrent rate, treatment of recurrence and outcome. About 35% of Bartholin gland carcinoma were squamous cell carcinoma. Almost 50% of patients presented with advanced stage. The therapeutic approach was mainly surgery, and in 61% of those women lymph node assessment was performed. Recurrence occurred in 21% of cases. Bartholin gland cancer remains a challenge for gynecologic oncologists. Guidelines, centralization to referral centers and standardized therapy are needed.

Aggressive Angiomyxoma of the Lower Female Genital Tract in Pregnancy: A Review of the MITO Rare Tumors Group.

Deep (aggressive) angiomyxoma of the lower genital tract is a rare malignancy affecting women of reproductive age. Being a hormone-sensitive tumor, its growth is particularly benefitted during pregnancy. Surgical excision with complete resection is indicated, even if a wait-and-see approach can be considered until delivery, to avoid destructive surgeries. The mode of delivery is to be evaluated based on the location and size of the neoplasm; vaginal delivery is not contraindicated, as long as the tumor does not obstruct the birth canal. Positive surgical margins are the most important prognostic factor for recurrence. Adjuvant therapy with gonadotropin-releasing hormone analogues may be proposed after pregnancy, in the case of non-radical surgery. Despite the high local relapse rate, the outcomes for mother and child are favorable. Since recurrences can occur after many years, the patient should be included in long-term follow-up.

The prognostic value of CD3+ tumor-infiltrating lymphocytes for stage II colon cancer according to use of adjuvant chemotherapy: A large single-institution cohort study.

BACKGROUND: High tumor infiltrating lymphocytes (TILs) density was previously shown to be associated with favorable prognosis for patients with colon cancer (CC). However, the impact of TILs on overall survival (OS) of stage II CC patients who received adjuvant chemotherapy (ADJ) or not (no-ADJ) is unknown. We assessed the prognostic value of CD3+ TILs in stage II CC patients according to whether they had ADJ or not. METHODS: Patients treated with curative surgery for stage II CC (2002-2013) were selected from the Santa Maria alle Scotte Hospital registry. TILs at the invasive front, center of tumor, and stroma were determined by immunohistochemistry and manually quantified as the rate of TILs/total tissue areas. High TILs (H-TILs) was defined as >20%. Patients were categorized as high or low TILs (L-TILs) and ADJ or no-ADJ. RESULTS: Of the 678 patients included, 137 (20%) received ADJ and 541 (80%) did not. The distribution of the 4 groups were: 16% (L-TIL/ADJ), 64% (L-TIL/no-ADJ), 5% (H-TIL/ADJ), 15% (H-TIL/no-ADJ). Compared to H-TILs/no-ADJ, ADJ patients showed a significantly increased OS (P<.01) regardless of the TILs rate whereas L-TILs/no-ADJ had significantly decreased OS and higher risk of death (HR=1.41; 95% CI, 1.06-1.88; P<.0001). On multivariable analysis, the unfavorable prognostic value of L-TILs (vs. H-TILs) for no-ADJ patients was confirmed (HR=1.36; 95% CI 1.02, 1.82; P=.0373). CONCLUSION: Low CD3+ TILs rate was associated with shorter OS in those with stage II colon cancer who did not receive adjuvant therapy. Low CD3+ TILs could be considered an additional risk factor for still ADJ-untreated stage II CC patients, which could facilitate clinical decision making.

Two-point-NGS analysis of cancer genes in cell-free DNA of metastatic cancer patients.

BACKGROUND: Although the efficacy of molecularly target agents in vitro, their use in routine setting is limited mainly to the use of anti-HER2 and antiEGFR agents in vivo. Moreover, core biopsy of a single cancer site may not be representative of the whole expanding clones and cancer molecular profile at relapse may differ with respect to the primary tumor. METHODS: We assessed the status of a large panel of cancer driver genes by cell-free DNA (cfDNA) analysis in a cohort of 68 patients with 13 different solid tumors at disease progression. Whenever possible, a second cfDNA analysis was performed after a mean of 2.5 months, in order to confirm the identified clone(s) and to check the correlation with clinical evolution. RESULTS: The approach was able to identify clones plausibly involved in the disease progression mechanism in about 65% of cases. A mean of 1.4 mutated genes (range 1-3) for each tumor was found. Point mutations in TP53, PIK3CA, and KRAS and copy number variations in FGFR3 were the gene alterations more commonly observed, with a rate of 48%, 20%, 16%, and 20%, respectively. Two-points-Next-Generation Sequencing (NGS) analysis demonstrated statistically significant correlation between allele frequency variation and clinical outcome (P = .026). CONCLUSIONS: Irrespective of the primary tumor mutational burden, few mutated genes are present at disease progression. Clinical outcome is consistent with variation of allele frequency of specific clones indicating that cfDNA two-point-NGS analysis of cancer driver genes could be an efficacy tool for precision oncology.

A case of eribulin-induced regression of liposarcoma of the left funiculus in a heavily pretreated patient.

We report the case of a heavily pretreated male subject affected by left funiculus liposarcoma and successfully treated with eribulin mesylate. After three surgical interventions, radiotherapy on the lesion of the penile bulb for satellite nodules and an epirubicin + ifosfamide chemotherapy treatment for six cycles, eribulin was administered at the dose of 1.1 mg/m2 on days 1 and 8, every 3 weeks for a total of nine cycles. A significant reduction of the lesions was achieved after four cycles of therapy, with a good profile of tolerability.

Feasibility of modified docetaxel, oxaliplatin, capecitabine followed by capecitabine as maintenance chemotherapy as first-line therapy for patients with metastatic gastric or gastroesophageal cancer.

The aim of this study was to evaluate the efficacy and safety of modified docetaxel, oxaliplatin, capecitabine (DOC) combination chemotherapy, followed by maintenance capecitabine as first-line therapy for patients with metastatic gastric or gastroesophageal junction (GEJ) cancer. Treatment consisted of docetaxel 35 mg/m (days 1-8), l-OHP 85 mg/m (day 1), and capecitabine 750 mg/m twice daily (days 1-14), every 3 weeks. After six cycles of DOC, patients who did not progress received maintenance treatment with three-weekly capecitabine 1000 mg/m twice daily (days 1-14), until disease progression or unacceptable toxicity. Six-month disease control rate (DCR) was the primary endpoint and overall survival (OS), progression-free survival (PFS) and safety were the secondary endpoints. The Kaplan-Meier method was applied to estimate OS and PFS. Between July 2014 and September 2017, 37 patients with metastatic gastric or GEJ cancer were enrolled at our institution. Upon completion of the DOC regimen, 35 patients (94.5%) received capecitabine as maintenance chemotherapy for a median of 7 cycles (range, 3-14 cycles). The six-month DCR was 83.7% [95% confidence interval (CI), 71.8-95.6%], median PFS was 8.2 months (95% CI, 6.3-9.8 months), and median OS was 14.4 months (95% CI, 11.7-18.6 months). During DOC chemotherapy, the most common grade 3-4 adverse events were neutropenia (29.7%), anemia (10.8%), and diarrhea (10.8%). During maintenance treatment, toxicity was sporadic and mainly of grade 1-2. Modified DOC followed by capecitabine as maintenance chemotherapy seems to be an active and well tolerated first-line treatment strategy for patients with metastatic gastric and GEJ cancer.

Gemcitabine plus nab-paclitaxel followed by maintenance treatment with gemcitabine alone as first-line treatment for older adults with locally advanced or metastatic pancreatic cancer.

OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of the combination Gemcitabine (Gem) plus nab-Paclitaxel (NabP) (Gem/NabP), followed by maintenance Gem in older adults with locally advanced or metastatic pancreatic cancer (PC). MATERIALS AND METHODS: In this prospective observational study, the induction chemotherapy consisted of NabP 125 mg/m2 followed by Gem 1000 mg/m2 on days 1, 8, and 15 of a 4-week cycle. After a maximum of 3 cycles, patients without evidence of progressive disease (PD) were administered Gem 1000 mg/m2 weekly for 3 of 4 weeks as maintenance therapy until documentation of PD or unacceptable toxicity. The primary endpoint was six-month disease-control rate (DCR). RESULTS: Overall, 36 patients >70 years with metastatic or locally advanced PC were enrolled at participating Institutions. After completion of Gem/NabP, 18 (50%) patients achieved partial response, 13 (36%) had stable disease, and 5 (14%) had PD. Thirty-one patients (86%) received Gem monotherapy as maintenance treatment for a median of 3 cycles (range, 2-9 cycles). Six-month DCR was 61% (95% CI, 45-77), median PFS was 6.4 months (95% CI, 5.4-8.3), and median OS was 13.4 months (95% CI, 11.1-16.7). During Gem/NabP regimen, the most common grade 3 toxicity included neutropenia (22%), anemia (19%) and thrombocytopenia (8%). Grade 3 neuropathy was not observed. During Gem maintenance therapy, grade 3 hematological toxicity was described in 6 patients (19%). CONCLUSION: Gem/NabP followed by maintenance Gem appears to be safe and effective for older patients with locally advanced or metastatic PC.

Capecitabine Plus Oxaliplatin and Bevacizumab, Followed by Maintenance Treatment With Capecitabine and Bevacizumab for Patients Aged > 75 Years With Metastatic Colorectal Cancer.

BACKGROUND: The aim of the present study was to evaluate the efficacy and safety of the combination of CAPOX-Bev (capecitabine [Cap] plus oxaliplatin and bevacizumab [Bev]), followed by maintenance Cap and Bev, for patients with metastatic colorectal cancer (mCRC) and aged > 75 years. PATIENTS AND METHODS: The regimen consisted of intravenous oxaliplatin 130 to 100 mg/m2 on day 1, oral Cap 750 to 1000 mg/m2 twice daily on days 1 to 14, and Bev 7.5 mg/kg on day 1, every 3 weeks. After 4 cycles of CAPOX-Bev, the patients without evidence of disease progression received maintenance treatment with Cap 1000 to 1250 mg/m2 twice daily on days 1 to 14 and Bev 7.5 mg/kg on day 1, every 3 weeks, until disease progression or unacceptable toxicity. The primary endpoint was the 9-month disease control rate. Progression-free survival (PFS), overall survival (OS), and safety were the secondary endpoints. RESULTS: Overall, 36 patients were enrolled from March 2012 to April 2017 at our institution. After completion of CAPOX/Bev, 15 patients (41.7%) had a partial response, 18 (50.0%) had stable disease, and 3 (8.3%) had progressive disease. Thirty-three patients (91.7%) received the Cap/Bev regimen as maintenance treatment for a median of 8.6 cycles (range, 3-14 cycles). The 9-month DCR was 58.3% (95% confidence interval [CI], 40.8-74.5), the median PFS was 8.8 months (95% CI, 6.7-10.3 months), and the median OS was 20.8 months (95% CI, 16.1-25.4 months). With the CAPOX/Bev regimen, the most common grade 3 toxicity included neutropenia (11.1%), diarrhea (5.5%), nausea/vomiting (2.8%), and fatigue (2.8%). Grade 3 neurotoxicity was not observed. With Cap/Bev maintenance therapy, grade 3 hand-foot syndrome was observed in 2 patients (6.0%). CONCLUSION: CAPOX/Bev, followed by Cap/Bev as maintenance treatment, is safe and effective in terms of PFS and OS for elderly patients aged > 75 years with mCRC.

Treatment of advanced oesophagogastric cancer with FOLFOX-4 regimen followed by leucovorin/bolus and continuous infusion 5-FU as maintenance chemotherapy in patients aged ≥ 75 years with impaired performance status.

OBJECTIVES: To evaluate the efficacy and safety of FOLFOX-4 combination chemotherapy, followed by leucovorin (LV)/bolus and continuous infusion 5-fluorouracil (5-FU) as maintenance chemotherapy in elderly (≥ 75 years) patients with advanced oesophagogastric cancer with impaired performance status (PS). MATERIALS AND METHODS: Patients with a PS score >1 were included in this study. PS evaluations were performed by a geriatrician and two medical oncologists. FOLFOX-4 consisted of oxaliplatin concurrently with LV/bolus and continuous infusion 5-FU every 2 weeks. After a maximum of six FOLFOX-4 cycles, patients with no evidence of disease progression received maintenance treatment with LV/bolus and continuous infusion 5-FU every 2 weeks until disease progression or unacceptable toxicity. RESULTS: Thirty-eight patients were enrolled in this study. Of these, 32 (84.2%) patients had a PS score of 2 and six (15.7%) patients had a PS score of 3. After completion of FOLFOX-4, 18 (47.3%) patients achieved a partial response and 14 (36.8%) patients had stable disease. Thirty-two patients (84.2%) received maintenance chemotherapy for a median of eight cycles (range one to 26 cycles). The 6-month disease-control rate was 47.3% [95% confidence interval (CI) 30.9-64.1]. The median progression-free survival was 5.9 months (95% CI 4.7-6.8) and the median overall survival was 9.6 months (95% CI 8.1-11.7). Grade 3 neutropenia occurred in six patients (15.7%), and Grade 3 anaemia and thrombocytopenia occurred in two patients (5.2%). CONCLUSION: FOLFOX-4 followed by LV/bolus and continuous infusion 5-FU as maintenance chemotherapy seems to be an active and well-tolerated first-line treatment strategy for elderly patients with advanced oesophagogastric cancer and impaired PS.

Maintenance treatment with oral cyclophosphamide and bevacizumab in patients with recurrent epithelial ovarian cancer.

AIM: To evaluate the efficacy and safety of maintenance treatment with oral cyclophosphamide (Cy) and bevacizumab (Bev) in patients with recurrent ovarian cancer. PATIENTS & METHODS: Induction treatment consisted of cisplatin, epirubicin, Cy and Bev every 3 weeks, for a maximum of six cycles. Maintenance treatment consisted of oral Cy 50 mg, days 1-14 and Bev 15 mg/kg, every 3 weeks until disease progression occurred. RESULTS: In total, 39 patients were enrolled: after induction chemotherapy, the objective response was 74.3%. The median progression-free survival was 13.3 months, and the median overall survival was 33.2 months. Toxicity during maintenance treatment was mild. CONCLUSION: Maintenance with Cy and Bev may achieve encouraging results in terms of progression-free survival and overall survival in recurrent ovarian cancer patients.

Carboplatin, methotrexate, vinblastine, and epirubicin (M-VECa) as salvage treatment in patients with advanced bladder cancer: a phase II study.

The primary objective of this study was to determine the activity and safety of carboplatin, methotrexate, vinblastine, and epirubicin (the M-VECa regimen) in patients with advanced bladder cancer after failure of at least one chemotherapy line. Treatment consisted of carboplatin 250 mg/m on day 1, methotrexate 30 mg/m on days 1 and 22, vinblastine 3 mg/m on days 2 and 22, and epirubicin 50 mg/m on day 2 every 28 days until disease progression or death. Response rate was the main end-point. Twenty-five patients were enrolled: the median age was 67 years (range 42-83) and there were 14 patients aged at least 70 years (56%). Fourteen patients had previously received vinflunine as a second-line treatment. Complete remission occurred in one patient (4%), partial remission in five patients (20%), and stable disease in eight patients (32%). The overall response rate was 24% [95% confidence interval (CI), 9.3-45.1%] and the overall disease control rate was 56% (95% CI, 34.9-75.5%). The median progression-free survival was 5.1 months (95% CI, 3.9-6.4) and the median overall survival was 9.5 months (95% CI, 7.1-11.2). Treatment was well tolerated: grade 3 neutropenia was documented in five patients and grade 3 nausea and vomiting in two patients. The M-VECa regimen seems to be feasible as second-line or third-line treatment in patients with advanced bladder cancer who have been pretreated with one or more chemotherapy lines, and may achieve encouraging results in terms of disease control rate, progression-free survival, and overall survival.

Reduced Dose of Abiraterone Acetate with Concomitant Low-dose Prednisone in the Treatment of ≥ 85 Year-old Patients with Advanced Castrate-resistant Prostate Cancer.

AIM: The aim of the study was to evaluate the activity and safety of reduced-dose abiraterone acetate (AA) in ≥ 85 year-old patients with advanced castrate-resistant prostate cancer (CRPC). PATIENTS AND METHODS: Patients received 750 mg oral AA as three 250-mg tablets once daily, with concomitant oral prednisone, 5 mg daily. RESULTS: Twenty-six patients were enrolled; median age was 88 years (range=85-93). Prostate-specific antigen (PSA) response was observed in 18 (69.2%) subjects, median time to PSA progression was 6.4 months (95% confidence interval (CI)=2.8-8.8) and median overall survival was 14.3 months (95% CI=7.2-18.3). The treatment was well-tolerated and adverse events, related to mineralocorticoid excess, were of grade 1-2 in all patients. CONCLUSION: Reduced dose of AA combined with a very low dose of prednisone is effective and well-tolerated in very elderly patients with advanced CRPC.

Rechallenge of docetaxel combined with epirubicin given on a weekly schedule in advanced castration-resistant prostate cancer patients previously exposed to docetaxel and abiraterone acetate: a single-institution experience.

The aim of this paper was to evaluate the activity and tolerability of weekly docetaxel (D) combined with weekly epirubicin (EPI) in patients with advanced castrate-resistant prostate cancer (CRPC) previously exposed to D and abiraterone acetate (AA). Locally advanced or metastatic CRPC patients with 0-2 performance status, who had progressed after D and AA therapy, were included in the study. Previous treatment with chemotherapy agent cabazitaxel was also admitted. Treatment consisted of D 30 mg/m(2) intravenously (i.v.) and EPI 30 mg/m(2) i.v., every week (D/EPI). Chemotherapy was administered until disease progression or unacceptable toxicity. In our institution, twenty-six patients received D/EPI: their median age was 72 years (range 59-83 years). Twenty-three (88.5%) patients had bone metastases. A decrease in PSA levels ≥50% was observed in seven patients (26.9%, 95% CI: 0.11-0.47); of these, five had achieved a ≥50% PSA response during prior first-line D and six had achieved a PSA response during prior AA Among the subjects who were symptomatic at baseline, pain was reduced in nine patients (38.1%) with a significant decrease in analgesic use. Median progression-free survival was 4.4 months (95% CI, 3-5.2), and median overall survival was 10.7 months (95% CI, 8.9-18.4). Treatment was well tolerated and no grade 4 toxicities were observed. Our findings suggest that weekly D/EPI is feasible and active in heavily pretreated advanced CRPC patients and seem to support the hypothesis that the addition of EPI to D may lead to overcome the resistance to D in a subgroup of patients.

CEA and CA19.9 as early predictors of progression in advanced/metastatic colorectal cancer patients receiving oxaliplatin-based chemotherapy and bevacizumab.

We evaluated the changes of the tumor markers CEA and CA19.9 as early predictors of progression in metastatic colorectal cancer (mCRC) patients participating in a clinical study and receiving chemotherapy and bevacizumab (Bev). Seventy-two patients had high baseline CEA or CA19.9 serum levels. By ROC analyses, the areas under the curves were 0.83 for variable CEA cutoff values for distinguishing progressive disease (PD) versus stable disease (SD)/partial remission (PR)/complete remission (CR), and 0.80 for variable CA19.9 cutoff values for distinguishing PD versus SD/PR/CR. Rises in CEA and CA19.9 may early signal the occurrence of progression in mCRC patients receiving chemotherapy and Bev.

Bevacizumab and weekly docetaxel in patients with metastatic castrate-resistant prostate cancer previously exposed to docetaxel.

Background. The aim of this paper was to evaluate the activity and tolerability of docetaxel (D) and bevacizumab (Bev) in patients with metastatic castrate-resistant prostate cancer (CRPC) previously exposed to D. Methods. Treatment consisted of D 30 mg/m(2) i.v. for four consecutive weekly administrations followed by a 2-week rest interval, in addition to Bev 5 mg/kg i.v. every 2 weeks. Results. Forty-three patients were enrolled: a PSA response was observed in 27 patients (62.7%, 95% CI: 0.41 to 0.91), and a palliative response was achieved in 31 patients (72.1%, 95%CI: 0.48 to 1.02). After a median followup of 11.3 months, only five patients had died. The regimen was generally well tolerated. Conclusion. Weekly D + biweekly Bev seems to be an effective and well-tolerated treatment option for patients with metastatic CRPC previously exposed to D-based chemotherapy.

Osteonecrosis of the jaw in patients with cancer who received zoledronic acid and bevacizumab.

BACKGROUND: The authors investigated the incidence of and risk factors for osteonecrosis of the jaw (ONJ) in patients with metastases to the bone who received the bisphosphonate agent zoledronic acid (ZOL) and chemotherapy combined with the antiangiogenic agent bevacizumab (BEV). METHODS: The authors evaluated 59 participants (34 with breast cancer and 25 with nonsmall-cell lung cancer). All of the participants received 4 milligrams of ZOL via intravenous (IV) infusion every four weeks and 15 mg per kilogram of BEV every three weeks. They conducted a dental examination in participants at baseline and every three months until the patients died or were lost to follow-up. If needed, participants received periodontal disease treatment and underwent tooth extraction before they started receiving ZOL and BEV. RESULTS: The median time the participants received ZOL therapy was 18.8 months (range, 3.1-28.9 months); 36 participants (61.0 percent) received ZOL therapy for more than one year. The median time participants received BEV therapy was 16.7 months (range, 2.8-29.6 months). None of the participants required dentoalveolar surgery while undergoing cancer treatment. After a median follow-up period of 19.7 months, none of the participants developed bisphosphonate-related ONJ. CONCLUSIONS AND CLINICAL IMPLICATIONS: ZOL combined with BEV did not predispose to ONJ participants with cancer that had metastasized to the bone who underwent a baseline dental examination and preventive dental measures. The study results must be considered in the context of the study's protocols and the follow-up period.

Effects of intravenous zoledronic acid and oral ibandronate on early changes in markers of bone turnover in patients with bone metastases from non-small cell lung cancer.

BACKGROUND: The aim of this study was to assess the early effects of zoledronic acid (ZOL) and oral ibandronate (IBA) on the bone resorption marker s-CTX (serum C-telopeptide of collagen type I) and the bone formation marker B-ALP (bone-alkaline phosphatase) in patients with bone metastases from non-small cell lung cancer (NSCLC). METHODS: Fifty-five patients with at least one site of bone metastasis secondary to NSCLC were randomly assigned to receive intravenous ZOL 4 mg every 4 weeks, or oral IBA 50 mg/day. RESULTS: At 1 month of treatment, s-CTX was reduced by 54.8% (95% CI 40.4-59.8%) in the ZOL group (26 evaluable patients) compared with 38.2% (95% CI 29.8-48.7%) in the oral IBA group (27 evaluable patients) (p = 0.03). At 3 months, s-CTX was reduced by 72.6% (95% CI 58.6-71.3%) in the ZOL group, compared with 66.4% (95% CI 54.3-79.5%) in the oral IBA group (p = 0.22). Both bisphosphonates similarly decreased the bone marker B-ALP at 1 month (ZOL 24.7%, 95% CI 3.6-39.5%, and IBA 24.2%, 95% CI 2.8-43.4%) and 3 months (ZOL 28.6%, 95% CI +2.8-43.3%, and IBA 24.2%, 95% CI 3.2-47.4%). Both bisphosphonates were well tolerated. CONCLUSION: Considering the changes in bone markers, ZOL and oral IBA show comparable efficacy in patients with NSCLC and bone metastases.

Second-line treatment of non small cell lung cancer by biweekly gemcitabine and docetaxel +/- granulocyte-macrophage colony stimulating factor and low dose aldesleukine.

Background. The antitumor activity of a novel biweekly gemcitabine (G) + docetaxel (D) regimen +/- granulocyte-macrophage colony stimulating factor (GM-CSF) and aldesleukine (IL-2) has been evaluated in a phase II trial in advanced pretreated non-small-cell lung cancer (NSCLC). Results. The treatment was well tolerated. The 42.3% response rate exceeded the predefined target activity, while time to progression (TTP) and overall survival (OS) were 7 and 11.2 months, respectively. A greater objective response rate (58.3% vs 28.6%) and an increased number of eosinophils, basophils and activated mononuclear blood cells were observed in those patients who also received cytokine administration. Methods. Twenty-six NSCLC patients received second line G (1000 mg/m2) and D (75 mg/m2) every 15 days. 12/26 patients also received s.c. GM-CSF (100µg, days 2-6) and s.c. IL-2 (0.5MIU/ twice daily, days 7-14 and 16-29) by random selection. Conclusion. The biweekly GD regimen is a safe and active second-line treatment in NSCLC. Addition of immune-adjuvant cytokines' may enhance the activity of this therapeutic combination.